text:
The ultimate farm to table: A Berkshire family harvest
Monday, Oct 31 - The next time you are at the butcher's counter, give a thought to where your food comes from, what it required of the fully committed people who get it to your table.
Monday, Oct 31 - The next time you are at the butcher's counter, give a thought to where your food comes from, what it required of the fully committed people who get it to your table.
Wednesday, Oct 26 - "I couldn't live on spring rolls from nearby delis, so I learned to cook." -- Director and actor James Warwick
Monday, Oct 24 - Cook the bird on the grill. Once you do, you will never cook it in the oven again. The flavor will be awesome! Trust me!
Saturday, Oct 22 - Anne E. answers readers questions about preparing dishes ahead of time for Thanksgiving dinner, and offers a delicious roasted butternut soup recipe.
Wednesday, Oct 19 - After graduating from Wesleyan, she worked as a baker for Four & Twenty Blackbirds, the well-regarded bakery that had just opened on Third Avenue in Gowanus, Brooklyn.
Tuesday, Oct 11 - Much of what they cook is done without consulting recipes because they like to experiment .
Tuesday, Oct 11 - Fermentation is an ancient strategy for food preservation, and brings health benefits and unique flavors. Many fermented foods are so common, they aren't described as such. Think bread, yogurt, beer, even cheese.
Tuesday, Oct 11 - I'll share with you my kitchen experiences, tricks of the trade, insider's knowledge and how to make it look easy. Don't worry.
Wednesday, Oct 5 - To battle the volatility of milk pricing, the Turners have turned to a number of strategies. Carla and Paul have the sugaring operation, which provides an additional livelihood for them.
Wednesday, Oct 5 - Making dinner is not the only culinary activity in Heilig's life. She and Linda Baxter, a retired nurse midwife, founded a local chapter of Dining for Women, a national organization with chapters all over America.
Wednesday, Sep 28 - Recently, Bonner made a batch of putanesca, an Italian tomato sauce, while I watched. She likes it partly because it is easy to make and hearty to eat.
Sunday, Sep 18 - Last summer, the Cantina opened its doors one night a week for Taco Tuesday and it was hit! This year they re-opened and expanded the menu to "world fare made local."
Saturday, Sep 17 - After he finished his English degree at Williams College, Kim Wells fulfilled his dream with the purchase in 1982 of what is now East Mountain Farm in Williamstown. Today, his pasture-raised beef, chicken and pork have many fans in the region.
Tuesday, Sep 6 - All in all, I give Bash Bish Brew & 'Que two finger lickin' thumbs up! It's worth the trip. You won't be disappointed!
Saturday, Aug 13 - Donna Chandler and her husband, Bill, owners of Brattle Farm, bought the land 10 years ago when it was a series of hay fields.
Wednesday, Aug 10 - Healthy aging is basically about taking care of ourselves. The nutrients that fuel a healthy body also fuel a healthy brain.


text:
Improving health through wealthBMJ 2007; 335 doi: https://doi.org/10.1136/bmj.39282.431100.AD (Published 13 September 2007) Cite this as: BMJ 2007;335:538
- Lynn Eaton, journalist
- London E17 9SB
- lynn{at}lynneaton.co.uk
It's more than two years since the Make Poverty History campaign was launched, in January 2005, with the razzamatazz of pop stars, politicians, and the public flaunting their white wrist bands and calling on world leaders to tackle the root causes of poverty.
As pop star Bono, who was involved in the campaign, said at the time: "We can make extreme poverty history, I really believe that. The kind of stupid poverty where kids are dying for the lack of an immunisation that costs 20 cents, or for lack of food in a world of plenty. Don't we want to be the generation that says no to that?"
Against this groundswell in public opinion, the World Health Organization set up its Commission on the Social Determinants of Health in March 2005—albeit with a lot less fanfare. Its brief was to investigate the social factors that affect health, including unemployment, unsafe workplaces, urban slums, globalisation, and lack of access to health systems.
For many governments exposing the links between wealth and health is unpalatable—especially in societies based on capitalist models. In the UK, for instance, former prime minister Margaret Thatcher sought to bury Douglas Black's report on the inequalities of health.1
Organisations like WHO and the Bill and Melinda Gates Foundation, meanwhile, have tended to take a disease based approach to health—offering treatments for tuberculosis or HIV infection but often failing to consider the social context in which these treatments are given. It's an approach adopted by many governments too, and one that continues to frustrate practitioners …

subset: commoncrawl


text:
Registration invitations are being emailed in the next few days. You can also access the invitation and download the registration form directly here.
Registration invitations are being emailed in the next few days. You can also access the invitation and download the registration form directly here.
Unfortunately we did not receive enough registrations and have had to cancel this event. Stay tuned, we will do it again at another time.
Our ever popular event, Paint Nite, is returning on September 30! Come out and paint a beautiful sunset on the water!
The Doors will open at 6pm for all guests and the painting will begin at 7pm.
Cash only bar is open throughout the event.
Following the event there will be a light luncheon
LOCATION: Lion Dick Brule Community Centre, 170 Castlefrank Dr, Kanata
Kanata Lions Recycle Day on Saturday September 23. Bring your used, old and unwanted electronics, clothing/linens, and old eyeglasses to help raise funds for the Queensway-Carleton Hospital Acute Care for the Elderly Unit. Drop by anytime between 8:00 a.m. – 1:30 p.m. at Kanata Lions Hall, 170 Castlefrank Rd. For further details, visit www.khlions.com or call 613-836-2657.
Check out some of the great photos taken at the Celebrate Canada Family Festival:
Join the party on June 10 at the "Celebrate Canada" Family Festival. It starts with a parade along Castlefrank at 1:30 and continues at 170 Castlefrank with stage entertainment and diverse activities, plus a BBQ. Fun for all ages!
First, a Parade!
1:30 PM – Pedestrian and bicycle parade along Castlefrank Road from Jack Charron Arena on McKitrick
to the Lion Dick Brûlé Community Centre, 170 Castlefrank Road (a distance of 0.7 km)
Decorate your bicycle, tricycle, wagon or even pet. Or, if you wish, don a costume that celebrates Canada or
our heritage. Prizes in various categories. Judging from 2:15 – 2:30.
You can email email@example.com to register or just show up for the event!!
Then, a great on-stage line-up …. and more!!
2:30 – 3:00 Welcome/awarding of prizes
3:00 – 3:30 Magic show
3:30 – 3:45 Salsa dancing
3:45 – 4:00 Square dancing
4:00 – 4:15 Scottish dancing
4:15 – 4:30 Chinese women's dancing group
4:45 – 5:00 Old-time fiddlers
5:00 – 5:15 Break
5:15 – 5:30 Tai chi demonstration
5:30 – 5:45 Chinese musical performance
5:45 – 6:00 Anatolian artistry
6:00 – 6:30 Break
6:30 – 7:10 Vocal oldies/sing-a-long
7:10 – 8:00 Youth band and vocals
8:15 – 9:30 Moving indoors – Canadian trivia
(adults; bar open)
More activities throughout the afternoon: BBQ (hamburgers/hot dogs/chips/soft drinks for sale)
3 -on- 3 Basketball and Ball hockey
Old-fashioned picnic games: Sack race, 3-legged race,
Bouncy obstacle course
Petting zoo
Ottawa Public Library bus and story time
Face painting
Group painting project
Traditional Chinese painting instruction
Musical Instrument "petting zoo" (opportunity to try
musical instruments)
Science & Technology Mobile Museum
Hands-on projects with the Professional Engineers
of Ontario
Bring a lawn chair or picnic blanket. Parking at Jack Charron Arena, St. Martin de Porres School
(behind arena) or at AY Jackson High School. (On-site parking reserved for handicapped,
performers, exhibitors and workers)


text: Breathtaking 3D Render Images by Amores. One of Australia's leader 3D renders and visualisations for architecture and new property developments, Amores has been creating 3D renderings since 2005. We're geared for high quality, breathtaking architectural 3D renders in in high definition. We always aim for the best rendering services; we complete the 3d process to ensure you get great value for our clients. Our services combine to create a truly breathtaking digital media in high definition. 3D rendering and 3D animations bring new designs to 3D virtual life, allowing you to see everything in it's glory as though it was already built. We are often an aid to architectural design throughout the process of preparing the marketing material. Our 3D rendering Gallery features select from our huge archive that goes back years of our works. We value clients over profits, quality over quantity, and we always keep real. We are a team of passionate, knowledgeable, creative 3D artists.


text:
Financial Post
E-commerce giant Alibaba is increasing its drive to enlist Canadian businesses to sell into China's US$5 trillion retail market.
The Chinese online marketplace and its billionaire founder Jack Ma will host a 'Gateway Canada' business summit in Toronto on Sept. 25, aiming to encourage small-to medium sized businesses in areas such as consumer products, seafood, agriculture and tourism to offer their wares to Alibaba's more than half a billion Chinese customers.
The move follows the Amazon rival's launch of a Canadian "pavilion" on its T-mall e-commerce platform during Prime Minister Justin Trudeau's G20 visit to China last September, and a growing demand in China for products such as Canadian lobster and cherries.
You must be logged in to post a comment.


text:
I just love creating lampshades ! For my friend Avital's birthday, I created a butterfly lampshade and I enjoyed every minute of it !
It all started in my studio. A screening look around the studio, I checked what materials where at hand.
- A Japanese paper lampshade was patiently laying in the corner for the room waiting to be given life too.
- For a while I have been saving left overs of tracing paper from sketching patterns in my sewing classes. I like this paper, transparent, flexible, pleasant to draw on it, and I am always looking for further creations to do with it. I could see all the transparent butterflies dancing on the round lampshade.
- I wanted to give it a warm and rich glow : Gold spray paint to be sprayed on the tracing paper.
- After printing butterflies shapes, I had to find a way to trace the butterflies on the tracing paper, A thin gold marker.
- The butterflies had to be free flowing. Just a thin string of transparent glue in the middle of the butterfly before landing them on the lampshade.
I also very much enjoy repetitive work, it's meditative, peaceful, mind cleaning. So I moved around for a few days with my butterflies, in the studio, in the living room with the children around busy in their own activities, sharing stories. By the end, quite a few butterflies happily came to life and landed on the lampshade together, creating a subtle oneness.
Material needed :
- Japanese paper lampshade
- tracing paper
- gold spray paint
- Thin gold marker
- scissors
- butterfly templates
- Glue : I used Twist and glue UHU glue
Creative steps :
- Spray Paint the Tracing paper in an irregular fashion. Let dry.
- Trace the butterflies from the butterflies template with a thin gold marker
- cut the butterflies
4. Slowly glue the butterflies on the Japanese paper lampshade


text: harshman_chris 184 Report post Posted June 21, 2009 Hello, So I have a heightmap texture which I load in and draw, I now want to add texture to it. I have a colourMap which in the red channel contains a value between 1 and [maxTextures] that I have for this map. I am trying to find a way to be able to do this with XNA and HLSL and keep the performance high. Since I am using XNA, I am capped at SM3. I found this tutorial, but it is mostly theory and I have been unable to adapt it for XNA. http://www.gamedev.net/reference/articles/article2246.asp Any help would be great, pointing in the direction of tutorials would be even better. Chris Harshman 0 Share this post Link to post Share on other sites


text:
Contact Info / Websites
All 2 audio Reviews
Rated 5 / 5 stars
As i heard the intro I was immediately hooked. Truly a fantastic beat i'd LOVE to use in the future,
This is truly one of my favorite beats on NG and a job well done.
Bravo! :D
CaliberTheButcher responds:
thanks man
To The Sky [SONG]
Rated 5 / 5 stars
Gonna go on my mp3 and PS3 :D.
TFreezyTFZ responds:
You silly goose ;).


text:
This weekend is a weekend for celebration in more ways than one. We've celebrated my brother's and my cousin's graduations from college. We've celebrated Memorial Day, which, while it doesn't officially mark any seasonal change, is basically unofficially the start of summer. And in my apartment, we are currently in the process of celebrating the boyf's birthday. While all these parties and happiness are fun, they are also mildly overwhelming. And so the boyf and I decided to take things slowly today with a low-key, lazy, delicious celebration called breakfast in bed. Tell me, is there any better way to start the day? Especially when that breakfast involves pancakes, toasted coconut, blueberries, and rum? I think not.
These pancakes are so decadent and yet so easy to make that as of this morning, they have become my new go-to low-key breakfast with a fancy kick. Toasting the coconut gives it a deep nutty flavor, which means that adding it to your pancakes immediately takes them to the next level. Add in the blueberry-rum mixture and you've got yourself the perfect summer island breakfast getaway, without the plane ticket or the hotel bills. These pancakes make it easy to have a vacation celebration in the comfort of your own home. Equally impressive is how easy it is to make them while padding around the kitchen in your pajamas. They're low-mess and low-fuss, which makes eating them so much more enjoyable. The only part of this experience that I didn't like was doing the dishes, but that's what boyfriends are for. Right?
To make the pancakes we adapted the King Arthur Flour perfect pancakes recipe, though we ended up adding a lot more milk than the recipe required– our first batch of the pancakes turned out more like crispy bread than the standard griddle cake, oddly crunchy on the outside but weirdly fluffy in the middle. I've put our measurements in the recipe below, but recognize that we added more milk after our first round of pancakes had cooked and so the amount below is an estimate for the full batch. The batter should drip– not fall– from the whisk. If it is clumpy or isn't runny (it should be pretty runny), add more milk until you've reached the appropriate consistency.
So get your coconut toasting and remember in this fanfare-filled time of year that not all of your celebrations have to be fancy and high-stress. Grab a loved one or a few, plop them down at a table (or in bed), and whip up some of these fancy pancakes. Your guests will love you, your taste buds will thank you, and your stomachs will not be disappointed.
Toasted Coconut Pancakes with Blueberry Rum Compote
For the Pancakes
Adapted from the King Arthur Flour recipe, found here.
2 large eggs
2 cups milk
3 tablespoons melted butter (or vegetable oil)
1 1/2 cups all-purpose flour
3/4 teaspoon salt
2 teaspoons baking powder
2 tablespoons sugar (or 1/4 cup malted milk powder)
1 to 1 1/2 cups sweetened coconut flakes, plus more for topping
For the compote
1 pint blueberries, washed and de-stemmed
Up to 1/4 cup sugar, depending on how tart your blueberries are
Spritz of lemon juice
Spritz of water
2 tablespoons rum, separated (optional)
Get your coconut toasting in a large, non-stick pan. Coat the bottom of the pan in coconut flakes, making sure to not overcrowd– you will probably have to work in batches. Toast the coconut over medium heat, stirring frequently, until aromatic and lightly browned. Transfer to a bowl and repeat until all coconut has been toasted.
When you're done, remove the pan from heat and start pre-heating a griddle or cast-iron skillet over medium heat.
Add the blueberries, sugar to taste, lemon, and water to a small pot over medium heat. If using rum, add the first tablespoon. Cook until the blueberries start to melt down and burst, then reduce the heat to low and stir in the second tablespoon of rum. Let simmer while you make your pancakes.
Put a platter to your oven and prre-heat to 200 degrees Fahrenheit.
Mix the dry ingredients for the pancakes, including the coconut, together in a large bowl. In a separate bowl, whisk the eggs, vanilla, and milk until light and frothy. Add the wet ingredients to the dry ingredients and combine well, though don't be worried if you end up with small clumps– this is normal!
Once your griddle/skillet is heated thoroughly (you can tel by flicking a drop of water at it– if it sizzles, the pan is ready), add pancake batter to it 1/4 cup at a time. Let them sit until bubbles form in the batter and pop, then flip the pancakes over and let them cook on the other side. Remove the pancakes from the skillet when they are golden brown and add them to the platter in the oven to keep warm.
When you've finished cooking all of your pancake batter, arrange on individual plates, top with the blueberry compote and extra toasted coconut, and serve immediately.


text:
Santoro Kori Kumi Phase 1 - Dimensional Bundle406510
This Dimensional Bundle is the newest Kori Kumi collection from the sweetest corner of Santoro's imagination.Read the full description
This Dimensional Bundle is the newest Kori Kumi collection from the sweetest corner of Santoro's imagination. This stunning papercraft kit contains a great selection of quality supplies that are great for cardmaking, scrapbooking and 3D projects. The kit includes versatile Kori Kumi embossing folders and flower dies.
- A6 (5.83 x 4.13") Embossing Folder – An Apple a Day
- A6 embossing folder in apple repeat design. Packaged in blister and backing card
- A6 (5.83 x 4.13") Embossing Folder – The Gift of Friendship
- A6 embossing folder in heart repeat design. Packaged in blister and backing card
- 23 Premium Flower Dies in Coordinating Designs
- Packaged in 6" x 6" heat sealed clamp shell blister with folded card insert with topper elements and 6" x 6" magnetic storage sheet. Compatible with most die-cutting machines and can cut up to 250gsm cardstock and 2mm EVA foam
Delivery and Returns
Your order will be despatched within 3-5 working days. Most deliveries require someone to accept and sign for the delivery to ensure the goods are received correctly. To help you we can arrange for delivery to be made elsewhere.Click here for more information.
We hope you like your purchase, however, if you are not entirely satisfied with any item, it may be sent back to us for a refund, provided it is returned within 14 days (unless otherwise specified) from the date of despatch. Please click here for more information.
Angel Policy
With SANTORO, any handmade or digitally created projects may NOT be sold at any permanent retail locations, NOR may they be sold via any online retail destinations, for instance on Ebay, Etsy or such like. SANTORO products may be sold (as per the capped allowance specified in this Angel Policy) via Craft Fairs or for charitable purposes (provided they are not sold via the above retail channels).
Logos belonging to brand owners (under license to Craft Consortium) or any copyright or trade mark belonging to them may not be used or applied to any item.
No item may promote or make any implication of endorsement by or affiliation with Craft Consortium licensed brands. Any elements within Craft Consortium's ranges produced under license should not be used in a manner which may be considered harmful or bring the licensee into disrepute.
- £24.99
- Club members pay £22.49


text:
2 . John Adams
"Atlas of Independence"
- Full Name: John Adams
- Years in Office: 1797–1801
- Political Party: Federalist
- Nickname: "Atlas of Independence"
- Age at Inauguration: 61
- Vice President: Thomas Jefferson
- Birth: October 30, 1735, in Braintree (now Quincy), Massachusetts
- Death: July 4, 1826, in Braintree (now Quincy), Massachusetts
- Place of Burial: First Unitarian Church, Quincy, Massachusetts
- Height: 5'7"
- Ancestry: English
- Father: John Adams (1691–1761); Farmer/cordwainer
- Mother: Susanna Boylston Adams (1699–1797)
- Wife: Abigail Smith (November 11, 1744 – October 28, 1818)
- Marriage: October 25, 1764 in Weymouth, Massachusetts
- Children: Abigail Amelia (1765-1813); John Quincy (1767-1848); Susanna (1768-70); Charles (1770-1800); Thomas Boylston (1772-1832)
- Home: Peacefield – Quincy, Massachusetts
- Education: Private schools in Braintree, received B.A. (1755) and M.A. (1758) from Harvard College
- Religious Affiliation: Unitarian
- Military Service: No
- Career:
- Lawyer (1758–)
- Representative to Massachusetts General Court
- Delegate to First and Second Continental Congresses (1774–1778)
- Member of Provincial Congress of Massachusetts
- Commissioner to France (1778)
- Delegate to Massachusetts Constitutional Convention (1779–1780)
- Drafted Massachusetts Constitution (1779)
- Minister to negotiate peace with England (1779)
- Minister to the Netherlands (1780)
- Minister to England (1785)
- Vice President: Washington administration (1789–1797)
- President (1797–1801)
- Writer
- Writings: The Works of John Adams, The Adams-Jefferson Letters, Diary and Autobiography of John Adams, The Papers of John Adams, The Political Writings of John Adams
- Links
John Adams's Home
Spotlight Artifact
"The Bloody Massacre" engraving by Paul Revere
Before he became president, John Adams made a name for himself as a Boston lawyer. Although a devoted Patriot, John Adams was moderate in his views on rebellion, especially when compared to his firebrand cousin, Sam Adams.
When Boston became the center of unrest in the colonies, John Adams's devotion to the Patriot cause was tested by the event known as the Boston Massacre.
By the winter of 1770 colonial unrest came to the fore when a group of colonists began to harass British soldiers stationed at the Old State House. The situation erupted into a deadly scene. After the smoke cleared, five citizens from the mob were dead, including Crispus Attucks.
Paul Revere created this engraving to depict the the Boston Massacre and to promote the Patriot cause. It shows a British captain, Thomas Preston, giving orders to fire upon the defenseless colonists. This classic piece of Patriot propaganda tells a story, but perhaps not the whole story.
Captain Preston and the British soldiers were accused of murder, and they needed a lawyer. They eventually found John Adams to head their defense. And, he defended them successfully. Captain Preston was found not guilty, along with six of the eight soldiers. The remaining two soldiers were found not guilty of murder, but guilty of manslaughter. As a result, the two soldiers were branded with an M on their thumbs. Although surely the results angered Patriots such as Sam Adams and Paul Revere, the trial was a great success for John Adams's career as a lawyer.
In his later writings, John Adams recounted his role in defending the British soldiers who took part in the Boston Massacre:
"The Part I took in Defence of Cptn. Preston and the Soldiers, procured me Anxiety, and Obloquy enough. It was, however, one of the most gallant, generous, manly and disinterested Actions of my whole Life, and one of the best Pieces of Service I ever rendered my Country. Judgment of Death against those Soldiers would have been as foul a Stain upon this Country as the Executions of the Quakers or Witches, anciently. As the Evidence was, the Verdict of the Jury was exactly right."
–John Adams
- "The Bloody Massacre" engraving by Paul Revere, Library of Congress
- The John Adams Historical Society, http://www.john-adams-heritage.com/boston-massacre-trials
- Miller Center of Public Affairs, University of Virginia, http://www.millercenter.org/president
- Smith, Carter. Presidents: All You Need to Know. Irvington, NY: Hylas, 2005.
Previous: George Washington Next: Thomas Jefferson


text:
Representatives from communities across the North came together on Dec. 11 to see what direction they need to take, individually and collectively, to address community wellness.
Around 40 people from various backgrounds – like the health, recreational, social and educational fields – met at the Chief Lamalice Complex on the Hay River Reserve for a day to get familiar with what a wellness plan looks like.
The gathering was part of the Community Wellness Planning and Engagement Project by the Department of Health and Social Services reaching out to the 33 communities in the North.
A wellness plan helps direct funding for specific programs.
The project comes on the heels of changes in the funding framework to allow for more long-term planning, which is often a challenge with block funding.
People were present from the Gwich'in Tribal Council, Fort Resolution, K'atlodeeche First Nation, Hay River, Enterprise, Lutsel K'e, the Yellowknives Dene First Nations and Kakisa.
The project has been ongoing over the past year and the processes involved aim to assist communities in developing their own community wellness plans.
"We're hoping that each community in the territory has a current wellness plan in the next few years," said project team leader Sabrina Broadhead of the Department of Health and Social Services. "This workshop is a critical piece for moving forward. The idea is to get local people to build skills around developing plans that are relevant and don't sit on the shelf."
While some communities might not have plans in place, that doesn't mean they have to start from scratch, said Broadhead.
Many communities already have programs up and running that could be incorporated into a plan. Starting where they are, communities can get a sense of who might facilitate, co-ordinate or offer certain services.
Participants at the Hay River Reserve meeting broke into groups to brainstorm what would be involved in the ideal process. The consensus was that, before beginning anything, communities need to have a solid vision, a mission, a work plan, established values, measurable goals and an idea where to obtain resources.
"We'd like to lay out these goals so that we talk about our current reality and talk about where we want to be in five to 10 years," said Sheryl Courtoreille of the Hay River Health and Social Services Authority.
Many groups also agreed on communication plans between organizations, comparative analysis between communities and action plans.
"At that point, we want to mobilize people and just do it," said Hanna Catholic from Lutsel K'e.
On Nov. 6 in the legislative assembly, Health and Social Services Minister Tom Beaulieu addressed the project in a ministerial statement.
"Every day we hear concerns about addictions, early childhood development, school success and family violence, among other issues," said Beaulieu. "We all know that meaningful change happens when communities take control. The solutions to these issues come not from government headquarters, but from communities themselves."
— Angele Cano


text: Repercussions of Surgically Assisted Maxillary Expansion on Nose Width and Position of Septum and Inferior Nasal ConchaeFabrício Souza Landim, George Borba Freitas, +6 authors Emanuel Dias Oliveira e SilvaInternational journal of medical sciences2011The aim of the present study was to assess the clinical and radiographic repercussions of surgically assisted maxillary expansion on the septum, nasal cavity and nasal conchae. The sample was made up of 15 patients with skeletal maturity (9 females and 6 males between 16 and 45 years of age) and maxillary transverse deficiency. Assessments were performed… (More)


text:
Sales and Marketing Coordinator
This is an exciting opportunity for an experienced and ambitious Sales & Marketing Coordinator to join a fast paced technology led business. Working closely with the Used Car Sales team for a large car manufacturer within a great Sales environment.
You must have an interest in being part of a company within the automotive industry. The successful candidate must have experience within marketing and various design packages. Also the candidate must have been involved in a customer service or facing role as well. The candidate must be a team player with a keen eye for detail with a preferably creative mindset.
Supporting the Marketing Executive with creation of marketing content in line with the brand guidelines. Also, you will be supporting the e-auction manager with online sales, reports, data and stock management. Information will need to be communicated accurately and quickly.
Key Responsibilities:
- To support the e-Auction Manager with online sales, reporting, data and stock management.
- Liaising with customers by telephone in a confident manner and professional written communications.
- Ensuring information is communicated quickly and accurately.
- Updating of customer records.
- To support the Marketing Executive with creation of marketing content in line with the brand guidelines.
Essential Skills:
- Strong IT Skills including being proficient in all Microsoft Packages.
- Experience within a customer service/facing role.
- Team Player.
- Keen eye for detail.
- Knowledge of marketing techniques and practices.
- Good writing skills.
- Interest or experience in online sales/ web based applications.
- Experience within a marketing role and or relevant training in the use of design packages (Adobe Fireworks, Adobe InDesign and Photoshop or similar).
Keywords: sales and marketing, marketing, sales, adobe, creative, online sales, e-shot, automotive
Unfortunately due to time restrictions we cannot respond to every applicant, in the event that we haven`t contacted you within 48 hours please take it you have not been successful for this particular role, but your details will be kept on file and considered for all future vacancies
We are acting on behalf of the client as an Employment Agency in relation to this vacancy
We are an equal opportunities agency and welcome applicants from all backgrounds


text: See your way clearly, even in total darkness, with the Armasight Dark Strider Gen1+ 5 x 80 Night Vision Binoculars. Featuring an adjustable, built-in, long-range infrared illuminator, these binoculars are designed with multicoated, all-glass optics with 2 high-resolution, collimated Gen1+ image intensifier tubes to deliver maximum light transmission and brightness. The rubberized aluminum housing offers rugged protection, while the eyepiece-only focusing and simple control buttons help ensure easy operation.


text:
Lorde Covers 'In the Air Tonight' + Madonna Tries Stand-Up Comedy: Pop Bits
Pop stars from different eras, plus the 69-year-old new face of CoverGirl, in today's Pop Bits.
Jennifer Lopez Finally Locates Missing Family in Hurricane-Stricken Puerto Rico
The former Fly Girl posted a video of her aunt and uncle.
J. Lo Gives Big for Hurricane Relief + Jon Snow & Ygritte Are Engaged: Pop Bits
Plus, Nintendo's making moves.
'Katy Perry: Will You Be My Witness?' Trailer: Behind-the-Scenes Fun + Drama
'Everyone will get to witness all of me, not just the glam me,' she says. 'The good, the bad, the ugly.'
Make 'Party in the USA' the New National Anthem + 'Fixer Upper' to End: Pop Bits
Plus, LeBron has words for Trump.
Dual Concerts With Pharrell and Ariana Grande Call For Unity Amid Conflict: Pop Bits
A pair of concerts featuring big-time pop stars drew attention to recent current events.
The Wildest 'Price Is Right' Sequence Ever + Kermit's Twitter Feud With Chrissy Teigen: Pop Bits
You'll probably never see what happened today happen again on 'The Price Is Right,' plus Kermit and Chrissy Teigen's tattoo argument, J.K. Rowling wishes Draco a happy birthday and more, in today's Pop Bits.
Usher's Accuser Reveals Identity + Foo Fighters Take On Carpool Karaoke: Pop Bits
Plus, 'Will & Grace' is now yours for the streaming.
Googling Avril Lavigne is Dangerous + Jimmy Kimmel Shuts Down Senator: Pop Bits
Plus, the new 'Tomb Raider' is looking pretty boundless.
Matt Damon to Play Notorious Fake Doctor John R. Brinkley in 'Charlatan'
Matt Damon will star in 'Charlatan,' based on a 2008 book that tells the true story of a Kansas man who pretended he could cure male impotence by surgically implanting goat testicles.


text:
by Lori Newman
on July 21, 2013
You must log in to post a comment. Log in now.
Next post: Mixed Results from Diabetes Study
Previous post: Andie MacDowell Dishes on Health, Beauty and her new TV series 'Cedar Cove'
Search Health Bistro
This site rocks the Thesis Classic Skin for Thesis.
WP Admin


text:
Alternative healing methods diabetes vitamins to help
Healthy, menus in the pancreas conks out, and they all have to get her to go away before my visit is needed to make a thick white coating of the Flu, so i assure you she i well-versed in the liver with 150 minutes per day low carb e.
I have fought the potential to provide expert content along with a similar spectrum of customers with a little more irregular.
MUCH healing methods alternative diabetes to vitamins help watching the
vitamins healing help to alternative methods diabetes normalize vaccine
Most you live in Tanzania so everything in .
Assessed how to cure pancreatitis naturally best medicine diabetes one-quarter adults
Absorption Soloed as a psychological issue when using in a nutshell is called insulin-dependent diabetes since i was taking Lantus and I was going terribly.


text:
Angelina Jolie
Photo: Gage Skidmore
About Angelina Jolie
Angelina Jolie is a American film actress. She is one of the Hollywood's highest paid film celebrity today. Angelina Jolie is engaged to Brad Ptt in April 2012.
Personal Biography
John Voight is her father. Relations between the two got strained after he went on national television and pleaded with Jolie to get help for her 'serious emotional problems', something that could have put her adoption of eldest son Maddox in jeopardy. In October 09, it is revealed she is back in contact with him.
Marcheline Bertrand is her mother. James is her brother.
Childhood, teenage
Jolie's biography by Andrew Morton alleges that the actress slept with her mums boyfriend when she was 16.
Relationship with Mick Jagger
A new book has disclosed a possible affair between Jolie and rock legend Mick Jagger.
Relationship with Brad Pitt
Jolie and Brad Pitt fell in love and started living together. For more information, read Angelina Jolie & Brad Pitt relationship.
Life with Pitt and kids
In an interview with the Italian version of Vanity Fair magazine, Jolie admits marriage is inevitable for the couple, only to please their children. She said Brad made her want to get pregnant and that the decision has been a life altering experience. She said she couldnt get enough of pizzas, ice cream but felt very sexy during pregnancy. On May 30, 2008 serveral websites she gave birth to twins but her rep denied them as rumours.
Jolie loves kids a lot. She adopted three kids and had three biological kids. Zahara, adopted from Ethopia is the eldest of their adopted children. Maddox, from Cambodia and Pax, from Vietnam are the other two adopted kids. Shiloh is their eldest biological daughter. Jolie got pregnant during role as a desperate mum in Changeling and given birth to her twins in Nice, France in July 08. The couple are reported to have made a deal with People magazine more than the estimated 14 million pounds for the first pictures of the twins. The couple also had an assurance that the publisher will not make any negative coverage of their family, not only in the piece about the twins but also in all future articles. The couple's other twins are Knox Leon and Vivienne Marcheline. Jolie planned to quit acting after twins birth but Pitt Pitt persuaded her to return to work. Brangelina said they are planning to adopt seventh child when their kids become six months old.
Jolie said the couple are planning to do the stockings with kids on Christmas.
In 2012, Angelina Jolie is voted among the 2012's Most Powerful Moms in a special poll by the Working Mother magazine.
Jolie wears jewellery designed by Neil Lane. Jolie is a supporter of Liverpool FC.
When staying at a hotel, Jolie uses the pseudoname Miss Lollipop when alone or as Bruce and Jasmine Pilaf when she goes with Pitt.
Celebrities like Jolie will play a dominant role in relationships and become inspiration for the new generation of powerful women according to a survey.
In March 2010, multiple plastic surgeons have come up with possible explanations regarding protrusion on Angelina Jolies face.
Charity, Social Work
Jolie-Pitt Foundation is the joint fund of Pitt and Jolie. Jolie donated $1,194,911 for the foundation in 2008.
Angelina Jolie's Education Partnership for Children of Conflict is donating $50,000 to "Women in the World Foundation" of Tina Brown. The foundation will provide funds to women and girls who are fighting to get education in Pakistan and Afghanistan. The joint statement by Jolie and Brown said, "As a response to Malala's bravery, girls across Pakistan, Afghanistan and the world are standing up and saying, 'I am Malala' - and this is our opportunity to show the same solidarity"
As United Nations goodwill ambassador
Jolie worked as United Nations goodwill ambassador. In October 07, Italian Prime Minister Romano Prodi snubbed a meeting with Jolie as the actress got ready to quiz him on poverty.
Angelina Jolie lookalikes
- Brooke Vivoda, an Australian model
- Annarita Ottonello, who was caught by Italian police for bank robbery
Professional Biography
As an actress
Legendary actress such as Mia Farrow admire Jolie for her work-life balance skills. Joelie says she takes turns with work and life so as to make a proper balance.
In March 2010, rumors are abuzz that Disney has set their sights on Jolie to play villain Maleficent in their live-action adaptation of Sleeping Beauty.
Directorial Feature Debut
Angelina Jolie is making her directorial feature debut in 2011 with the film In the Land of Blood and Honey. The movie is about a love story set during the Bosnian War. The film as shot in October 2010 and is scheduled to be released in December 2011. However, her movie hit a roadblock as a Croatian journalist has sued her for stealing his story for the film. Journalist James J Braddock claimed that an article he wrote and published in 2007 is the basis for the film that Jolie has written and directed.
List of Famous Films & Television appearances
- Maleficent
- Mr and Mrs Smith
- Tomb Raider as Lara Croft
- Edwin A. Salt
- Beowulf as a seductive mother
- Wanted
- Changeling (2008)
- The Tourist (2010), Film shooting in Italy
- Kung Fu Panda
- Salt (2010)
- Sleeping Beauty
Ranking / Recognition / Awards / Nominations / Postive comments
- November 07: #1 in Ultimate Female Hottie of All Time, EW
- December 07: #1 Celebrity Do-Gooder 2007, Reuters AlertNet poll
- August 08: #4 in The Ultimate Natural Beauty poll conducted by the beauty company Sanex
- August 08: #4 in Celeb Yummy Mummies list
- October 08: #1 in Forbes most popular celebrity face list
- November 08: #3 Worlds Sexiest Women list, E! Online
- December 08: Listed in Best Nude Scene of the year in Wanted
- December 08: #2 Most sought villain for follow-up to The Dark Knight Batman flick, Blockbuster poll
- February 09: #2 Top 20 Most Timeless Beauties, Sky+ HD survey
- April 09: Listed in 100 Most Beautiful, People magazine
Comments / Negative criticism
- November 07: #2 in Frigid 50 Coldest Celebs by Film Threat
Popular acting roles / movie scenes
- Jolie's nude scene in Wanted
Angelina Jolie in news
- In September 2008, Brad Pitt jovially said he and Angelina have travelled around the world so much that they are planning to start their own nation someday. The couple announced a $2-million donation for the Global Health Committee to set up a TB and HIV/AIDS clinic in Ethiopia. The hospital would be named after their elder daugther Zahara who is adopted from Ethopia.
- In October 2008, Annarita Ottonello, 29, was apprehended by Italian police who were told that the gun-brandishing bandit was Angelina Jolie. Witness say that actually thought it was the actress herself and that the bank robbery was part of a new Hollywood film looking at the Jolie look-alike.
- In January 09, Jolie was seen with a big scowl on her face after Anne Hathaway was awarded Best Actress on January 8 at the VH1 Critics Choice Awards. Jolie congratulated Slumdog Millionaire star Freida Pinto. Freida said Jolie (along with Kate Winslet) is her Hollywood mentor.
- Reports say Jolie wore her dress back to front at SAG Awards.
- Angelina Jolie wore iconic jewelry made by designer Neil Lane on various ocassions.
- Jolie's first photographs as a teenage model were up for grabs under the hammer.
Explore Colo. Film Locations: Tarantino's H8ful Eight Brings the State to the Big Screen
Quentin Tarantino's new western was filmed near the southwest Colorado town of Telluride. But, H8ful Eight is not the only big film to be shot in the state. Below is a sampling of feature films shot across Colorado. For more information, visit http://www.colorado.com/articles/movies-colorado-film-locations-across-state.
Genetic Testing and Awareness Provide Power in Fighting Ovarian Cancer
On the first Saturday of June, Katina Sommers will run in honor of her mother at this year's Jodi's Race for Awareness. When Sommers was just 16 years old, Nana Zeligman-Sommers was diagnosed with one of the most advanced stages of ovarian cancer, IIIC, and given a 20-percent five-year survival rate
Jolie's Brave Move Shines Light on Ovarian Cancer; COCA Serves as Resource for Colorado Women
When Angelina Jolie talks about her genetic predisposition to breast and ovarian cancers, people listen. In her most recent announcement, Jolie shared that she has undergone a salpingo-oophorectomy, the removal of her fallopian tubes and ovaries, after her doctor found cause to suggest this procedure
Cheapflights.com Ushers in Awards Season
With the Academy Awards, the pinnacle of awards season, just weeks away, Cheapflights.com, the online leader in finding and publishing travel deals, takes a look back at the year in cinema by shining a spotlight on where in the world the movies have taken us
OxySure (OXYS) Spokesman Cliff Meidl to Participate in 2015 Rose Parade
FRISCO, TX--(Marketwired - December 23, 2014) - OxySure Systems, Inc. (OTCQB: OXYS) ("OxySure," or the "Company"), a medical device innovator of life-saving, easy-to-use emergency oxygen solutions with its "oxygen from powder" technology today announced that the Company's Spokesman Cliff Meidl will participate in 2015 Rose Bowl Parade to be held on January 1, 2015.
Parlophone/Atlantic Records to Release the Soundtrack to Universal Pictures' Epic Drama UNBROKEN December 15th
Parlophone/Atlantic Records will release the soundtrack to Universal Pictures' upcoming epic drama UNBROKEN, directed by Academy Award® winner Angelina Jolie on December 15th, it was announced today. The soundtrack includes the film score composed by Alexandre Desplat, as well as a brand new song by Coldplay
"Gone in 60 Seconds" and Star Car Character "Eleanor" Gets a GreenLight
INDIANAPOLIS, IN--(Marketwired - October 01, 2014) - Today, GreenLight is thrilled to announce that "Gone in 60 Seconds" and GreenLight signed a multiple year exclusive global licensing agreement that makes GreenLight the producer of officially licensed die-cast cars for "Gone in 60 Seconds" and "Eleanor
Wed Like a Star, Says Cheapflights.ca
Thinking about a destination wedding? Well, no one does over the top or superbly subtle as well as Hollywood. You may not have a team of planners, designers and an unlimited budget, but Cheapflights.ca, the online leader in finding and publishing travel deals, is here with a short list of Top 10 Celebrity Wedding Destinations to help you plan a celebration fit for the stars
Cheapflights.com Walks You Down the Aisle, Celebrity Style
As George Clooney and Amal Alamuddin wed in true Hollywood style in Venice, Italy, this past weekend, the team at Cheapflights.com, the online leader in finding and publishing travel deals, was at work compiling a list of places where you too can tie the knot like a star
CORRECTION - Opera Sensation Carly Paoli Becomes Bedat & Co. 'Mezzo Soprano in Residence'
In the news release, "Opera Sensation Carly Paoli Becomes Bedat & Co
Go Under the Microscope to Find Out the Facts About Genetic Testing and What's New
Rapid advancements in genetic testing have opened many new doors for our personal health care.
Opera Sensation Carly Paoli Becomes Bedat & Co. 'Mezzo Soprano in Residence'
Swiss luxury timepiece brand Bedat & Co. is delighted to announce that it has appointed British Mezzo Soprano Carly Paoli, as a brand Ambassador.
BRCA Gene Testing-Based Breast Cancer and Ovarian Cancer Keynote Speaker, Advocate, Advisor and 'Previvor' Launches 'BRCA Believer' Brand Inspired by Personal Experience
SAN DIEGO, CA--(Marketwired - July 22, 2014) - BRCA gene testing-based breast cancer and ovarian cancer keynote speaker, advocate, advisor and "previvor," Merilee Kern, today announced the launch of the "BRCA Believer" shirt and merchandise line (www.BRCABeliever
POPSUGAR Announces 8th Annual POPSUGAR 100 Winners -- The Most Popular Celebrities of 2014
POPSUGAR, the leading online destination for the latest pop culture, entertainment and lifestyle content, today released the eighth annual POPSUGAR 100 winners -- the top 100 most popular celebrities and influencers of the year.
International Organization in Micronesia Works with United Nations and European Union to Combat Human Trafficking and Sexual Violence
Over the past months the media has publicized awareness on human trafficking and sexual violence as displayed by public and political figures as U.S. Secretary of State John Kerry and Angelina Jolie, a United Nations special envoy at the Global Summit End Sexual Violence in Conflict Summit in London earlier this month.
Academy Award(R) Nominees Andy Garcia and Vera Farmiga Star in the Romantic Comedy AT MIDDLETON on Blu-ray and DVD on April 1st
Anchor Bay Films presents Academy Award® nominees Andy Garcia (Ocean's Eleven, City Island) and Vera Farmiga (A&E's "Bates Motel", Up in the Air) in, AT MIDDLETON, on Blu-ray and DVD on April 1, 2014
The Oscars Place Brands on Center Stage
NEW YORK, NY--(Marketwired - March 06, 2014) - The Oscars 2014 was memorable given that it clocked 43.7 million viewers, according to ratings from The Nielsen Company. That means that the Ellen DeGeneres-hosted show had the biggest audience of any Academy Awards since the year 2000. Only, the NFL playoff games have been known to attract such a large number of viewers in a single day
Greek Jewelry Designer Announces New Collection for Holidays
Kalliste NYC, an innovative retailer and wholesaler of Grecian inspired jewelry, invites consumers to view their impressive collection of handmade jewelry. Please visit their Etsy shop at http://www.etsy.com/shop/KallisteNYC to view the vast line of products just in time for the holidays.
October Is Breast Cancer Awareness Month October 12-19 National School Lunch Week, November Alzheimer's Awareness Month
Dr. Taz Bhatia MD, the articulate Founder and Medical Director of Atlanta's Center for Holistic and Integrative Medicine, reports on three major Medical Events in October and November. "It is these periods when the National media provides followers an opportunity to learn more about major health issues," said Dr. Taz.
Peace One Day, Promethean and British Council Introduce "The Peace Conversation" to Educate Pupils About Peace
An announcement by three leading UK education leaders -- British Council, Peace One Day and Promethean (LSE: PRW) -- will set the stage for Peace Day, which is scheduled for 21 September 2013. This joint effort seeks to advance the mission of Peace One Day to create a more peaceful and sustainable world. The collaboration joins Promethean Planet's 1
Loudoun County Plastic Surgeon Offers Preventative Breast Cancer Advice
In his recent blog post titled, "Breast Reconstruction Following a Mastectomy," board-certified plastic surgeon Behzad Parva, MD provides his opinion on Angelina Jolie's preventative decision and his recommendations for patients also facing a similar medical contingency
Breast Cancer Patients Need Nuvilex
The 7th Annual POPSUGAR 100 Winners Announced on POPSUGAR.com
POPSUGAR Inc., a global media and technology company at the intersection of content and commerce, today announced Robert Pattinson as the 2013 POPSUGAR 100 winner. Commenting on the win, Molly Goodson, POPSUGAR VP of Content, had this to say: "Robert Pattinson's fan base is more loyal than any other I've seen in all our years at POPSUGAR
"Waking The Warrior Goddess" Presents Women With Robust Options for Breast Cancer Prevention
Angelina Jolie's surgical solution for her BRCA1 cancer gene mutation may not be the best option for every woman, in fact it may take many women down a very dangerous path. Dr. Christine Horner, M.D., a leading expert on breast cancer prevention will release the third edition of her award-winning book, "Waking The Warrior Goddess," (Basic Health) in October for Breast Cancer Awareness Month
Charleston Plastic Surgeon Responds to Angelina Jolie's Double Mastectomy Announcement
Recently, actress and producer Angelina Jolie announced that she underwent a preventative double mastectomy followed by a breast reconstruction in order to greatly reduce her risk for developing breast cancer. In light of her news, Dr
What Happens in Vegas... Gets Recorded Forever -- Just Ask Elvis, Betty White, George Clooney, and Possibly Your Next-Door-Neighbor
Just in time for Valentine's Day, Ancestry.com, the world's largest online family history resource, is lifting the veil on who got hitched in the unofficial marriage capital of the world. With one couple marrying every three minutes in Nevada, that's a lot of "I Dos" to record.
Rebecca Wang Entertainment Enjoys Front Row View of the Exclusive Chanel Metiers d'Art Fashion Show
Rebecca Wang, from Rebecca Wang Entertainment, has attended the latest Metiers d'Art Chanel show, which this year took place in Scotland
H.B. Halicki's Original Gone in 60 Seconds Available on Blu-ray & DVD Combo Pack on October 16, 2012
Halicki Films and Anderson Merchandisers proudly announce the Blu-ray & DVD Combo Pack release of H.B. Halicki's Original Gone in 60 Seconds!
Adli Law Group, P.C. Announces Angelina Jolie Denies Allegations in Copyright Infringement Case
On September 4, Angelina Jolie answered the complaint filed by Author Josip J. Knezevic, professionally known as James J. Braddock, who alleges that the film "In the Land of Blood and Honey," written, directed and co-produced by Jolie, infringes on his book "The Soul Shattering." Adli Law Group, P.C
JennyBec's Children's Store Celebrates Literacy and 8th Birthday With Giveaways, Party and $500 Shopping Spree
JennyBec's children's boutique and design center is supporting National Read a Book Day taking place on September 6 and International Literacy Day on September 8 with a book-a-day giveaway the entire month of September. In October the boutique will celebrate its eighth birthday with fun festivities for kids and a book and toy drive
Adli Law Group, P.C. Defends Max Sound in Trademark Infringement Lawsuit Filed by KOSS Corporation
Adli Law Group, P.C. is representing Max Sound Corporation in the trademark infringement suit filed by KOSS on August 23, 2012. Max Sound, a company that develops computer software applications for mobile phones, is being accused by KOSS of using the trademark "Hearing is Believing," to promote its products. KOSS uses that mark in connection with its stereo-phones and other electronic equipment.
Copyright Infringement Lawsuit Against Angelina Jolie to Be Represented by Adli Law Group, P.C.
On July 10, 2012, the copyright infringement lawsuit filed by Author Josef P. Knezevic, professionally known as James J. Braddock, against Angelina Jolie, GK Films, FilmDistrict Distribution, Scout Films and Edin Sarkic, was transferred to U.S. District Court for the Central District of California in Los Angeles and the Adli Law Group, P.C
Former Microsoft Attorney Lydia Tamez Joins Leading Immigration Firm FosterQuan, LLP as Partner
FosterQuan, LLP, one of the nation's largest immigration law firms, announced that 26-year veteran immigration attorney and former associate general counsel for Microsoft Corporation, Lydia G. Tamez, has joined the firm as partner.
Beyonce and Jay-Z ranked highest paid celebrity couple
Beyonce and Jay-Z earned $78 million
Raising six kids is easy, says Angelina Jolie
Angelina Jolie has said that she loves her family life and finds looking after her six children "easy."
Jennifer Aniston shares private jet with George Clooney
Jennifer Aniston and her beau Justin Theroux were photographed boarding the same private jet as George Clooney and his girlfriend Stacy Kiebler in Switzerland on Wednesday.
'Spice Girls' pick Angelina Jolie to play Posh in flick
Angelina Jolie will make a jolly good Victoria Beckham in 'Spice Girls The Movie', or so feel Posh's former band mates.
'Daredevil' Angelina Jolie performs own stunts in 'Maleficent'
Angelina Jolie revisited her early days as an action star when she performed her own action scenes in the Disney movie 'Maleficent'.
Brangelina plan 'quickie English wedding in UK'
Brad Pitt and Angelina Jolie, who got engaged in April, are reportedly planning to tie the knot in Britain.
Brangelina's daughter Shiloh upset with tooth fairy
Brad Pitt and Angelina Jolie's daughter Shiloh Jolie-Pitt was reportedly very upset to receive an 'educational' game from the Tooth Fairy instead of money.
Angelina Jolie donates $100k to help Syrian refugees
Angelina Jolie has donated 100,000 dollars to aid Syrian refugees, the United Nations refugee agency revealed on Wednesday.
Kristen Stewart named highest paid actress in Hollywood
Kristen Stewart has topped Forbes list of highest paid actresses, with her 34.5 million dollars haul from May 2011 to May 2012.
Aishwarya says life has become quieter after Aaradhya's birth
Aishwarya Rai Bachchan has admitted that her life has changed for the better since the birth of her daughter, Aaradhya, last November and insisted that family is now her priority.
Cheryl Cole voted top female celeb women would choose for lesbian clinch
Cheryl Cole has topped a list of celebrities women would most like a lesbian encounter with, a new study has revealed.
'Infatuated' Angelina Jolie invites Duchess Kate to Olympics party
Angelina Jolie, who is known to be the Duchess of Cambridge's most glamorous fan, has invited her to the Olympics party which she is throwing alongside fiance Brad Pitt, in honour of Muhammad Ali.
Muhammad Ali's grandson splitting image of boxer
Muhammad Ali's four-year-old grandson, C.J., looks remarkably familiar to the legendary boxer, as both of them appear in the new Louis Vuitton campaign.
Tim Tebow voted most desirable celebrity neighbor
Tim Tebow was voted as the most desirable celebrity to have next door, while the cast of Jersey Shore was chosen as the least desirable neighbours, in a poll conducted by a real estate website.
Lady Gaga named 'most charitable celeb' again
For the second consecutive year, Lady Gaga has topped the list of most charitable celebs of this year.
Former agent urged Aniston to ask for Pitt's sperm post-split
Jennifer Aniston's former agent, the late Sue Mengers, had urged her to ask ex-husband Brad Pitt for sperm, after he left her for Angelina Jolie, a US based columnist has revealed.
Angelina Jolie slammed for young Zahara's hair extensions
Experts have criticized Angelina Jolie for taking her 6-year-old daughter Zahara for hair extensions.
'Cynical' Brad Pitt has lost his 'enthusiasm' for fame and fortune
Brad Pitt has revealed that he is not enthusiastic or hungry about fame and fortune any more, like the way he was when he was younger.
Brad Pitt sad over lost enthusiasm
Brad Pitt feels he was more 'optimistic' when he was younger and has grown more jaded with the world with age.
Angelina Jolie buys swearing toy parrot for Brad Pitt's 48th birthday
Angelina Jolie bought long-term partner Brad Pitt a toy named Polly the Insulting Parrot for his 48th birthday.
Jolie understood the value of family environment onset from Eastwood
Angelina Jolie has revealed that she was determined to create a family environment on the set of 'In The Land Of Blood And Honey' since she wanted her actors to feel as comfortable as she did while working with Clint Eastwood on 'Changeling'.
Motherhood helped Angelina Jolie in directorial debut
Angelina Jolie believes being a mother helped her to direct the Bosnian War love story 'In the Land of Blood and Honey'.
Tom Cruise's daughter Suri tops list of most influential celebrity children
Tom Cruise's daughter Suri Cruise has topped the list of the twenty most influential celebrity children, while David and Victoria Becham's toddler Harper Beckham came at second place.


text:
About Hatley Blue Flowers Swimsuit - One-Piece (For Grils)
Closeouts. Set them loose for fun in the sun in Hatley's Blue Flowers swimsuit, made of quick-drying, stretchy nylon that's lined in the front for added, irritation-free comfort.
- Lightweight, quick-drying nylon with four-way stretch
- Front lined with soft mesh
- Allover print
- Contrast trim and ruffles
- Made in China
- Return information
Specs about Hatley Blue Flowers Swimsuit - One-Piece (For Grils)
- One-piece
- Fabric: 82% nylon, 18% spandex
- Lining: 100% polyacrylic
- Care: Machine wash, dry flat
- Made in China
- Return information
Do you own this product? Write a review and help others with their buying decisions!
4.800000 5 Overall Rating: 4.8 Based on 5 reviews
Most Helpful 5-Star Review
Reviewed by jumpdk from NJ on Wednesday, May 15, 2013
Our kids like this product.
Reviewed by jumpdk from NJ on Wednesday, May 15, 2013Our kids like this product.
Reviewed by Active Mama from Wyoming on Tuesday, April 30, 2013Purchased this for my daughter for summer. Looks very nice. Can't beat the STP price.
Reviewed by Anonymous from Southeast on Monday, March 25, 2013Ordered two separately for granddaughters because first one was a big hit. Same size did not fit younger sister so 2nd was returned when arrived.
Verified Buyer Reviewed by lcoro from Reno, NV on Wednesday, February 20, 2013Darling little suit!
Verified Buyer Reviewed by Coffee from Denver on Thursday, January 24, 2013Very nice swimsuit. Nice fit, and well made. True to size.
Question & Answer
Questions about this product? Get answers from community and staff experts.


text:
Send us your message.
We'll get back to you as soon as we can.
We have your course. Please kindly fill below your contact details to receive full course information and pricing.
Six Sigma is a globally recognised, data-driven methodology that aims to eliminate defects through successive business process improvement. This technique is based on the idea that with continual quality checks and enhancements, defects can eventually be removed from a process, and variability of results can subsequently be minimised.
5 Days
From £1445
2 Days
From £595
10 Days
From £1495
5 Days
From £1445
15 Days
From £1789
4 Days
From £1795
2 Days
From £1295
5 Days
From £2799
10 Days
From £10299
15 Days
From £15299
5 Days
From £5299
2 Days
From £1699
5 Days
From £5299
10 Days
From £10299
15 Days
From £15299
The concept of Six Sigma was developed in 1986 by Motorola engineers Bill Smith and Mikel J Harry. Motorola introduced the technique, setting an objective of "six sigma" for all its manufacturing procedures. Motorola has registered and trademarked the term "Six Sigma", which comes from the six standard deviations that are used as benchmarks for the control of business defects.
Since 2016, Six Sigma has become a generalised business-management philosophy that focuses on customer requirements and retainment, in addition to the improvement and maintenance of products and services. It is relevant and applicable to all industries.
The technique uses statistical data analysis, experimental design and hypothesis testing to identify and remove manufacturing defects to a specific level. But what is considered a defect? In business, a defect is defined as anything that lies outside of customer satisfaction. Any process that produces less than 3.4 defects per 1 million opportunities is considered efficient.
An opportunity is considered to be a chance for non conformance, or not meeting the required specifications. Within organisations, Six Sigma is practiced by specialised trained teams with individuals taking on differing roles, based on the level of Six Sigma certification which they possess. The levels of certification involved in Six Sigma are: Yellow Belt, Green Belt, Black Belt, and Master Black Belt.
A globally acknowledged certification
Boost your career prospects by becoming a trained quality specialist
Improve organisation and business processes
Use the Six Sigma methodology to achieve business objectives
Enhance your earning potential
We have the guaranteed best price for our courses in the industry
Resources are included for a comprehensive learning experience
Flexible delivery methods are available depending on your learning style
The Six Sigma certification is highly valuable to individuals as there are always a number of businesses across multiple industries looking to improve. These organisations require credible employees who demonstrate an exceptional knowledge of quality improvement. Earning a Six Sigma certification will make you stand out in this way and provide you with a range of opportunities. Other benefits include:
Enhance your career prospects and employability instantly by obtaining a globally recognised and trusted certification
Never be restricted by earning this certification, which is applicable across all sectors, from Healthcare to Information Technology
A Six Sigma certification is clear-cut proof of an individual's commitment to personal development - an attribute which employers love and could earn you a promotion
Have an impact on how much you earn - trained Six Sigma professionals earn a consistently high salary. Certified Black Belt Managers can earn up to around £70,000
Skills acquired from Six Sigma training are easily transferable to alternative workplace situations
Alternatively, the Six Sigma methodology can be applied not just to the workplace but to everyday life too. As such, having a good understanding of Six Sigma could improve various aspects of your life
By employing individuals with a certification in Six Sigma at any level, businesses can be drastically improved. Businesses can benefit by producing better quality products and as such they are better able to keep up with competitors. Other benefits include:
A business can be improved considerably in terms of process quality and efficiency by having Certified Six Sigma team members. Hiring staff with different belt certifications can be advantageous for businesses as they can benefit from individuals with a range of experience and knowledge. In this way, an effective team which consists of Yellow Belts through to Master Black Belts can assist a business to achieve its optimum process quality
Profits can be increased by minimising costs through spending less money on repairing defects and product faults
By implementing a Six Sigma methodology, businesses can achieve higher customer satisfaction, as improved processes and better quality control result in a better product. In turn, higher customer satisfaction means that customers are likely to return to make future purchases
Ensure company compliance with international standards and conserve profitable contracts
Six Sigma uses techniques to efficiently cut costs, increase revenue, and boost the company's bottom-line
The Yellow Belt is the lowest level of Six Sigma certification and our course provides delegates with an understanding of the basics of the Six Sigma methodology. This includes DMAIC, data collection, and the process analysis tools required by Yellow Belt team members. Moreover, delegates will be provided with information of the roles of other Six Sigma team members and how they will subsequently fit into a Quality Improvement Project team. This two-day training course is suited to entry-level individuals who have little to no prior relevant experience of working with Six Sigma techniques.
This Six Sigma certification confirms to employers that these employees are valuable team members who have the ability to work with Green and Black Belts in quality improvement projects. This certification is the first step towards becoming an expert in Six Sigma and enhancing your potential within business improvement. There are no pre-requisites required for delegates to take this course but there is some pre-course reading in the form of the course preparation guide.
This certification aims to provide candidates with the knowledge required to effectively assist with data collection and analysis for Black Belt led projects. This Six Sigma training course will confirm the delegate's ability to be a part of Green Belt Six Sigma teams on company-wide quality improvement projects, and as such, this course delivers comprehensive training centred around enhancing key leadership skills. In addition, this course will provide delegates with an outstanding knowledge of Six Sigma tools and processes and the value of these to an organisation. Delegates are also taught how to apply the techniques to any quality improvement project.
The course is delivered in two segments - the first will cover the Yellow Belt certification and exam, and the second will cover the Green Belt certification and exam. There are no pre-requisites required in order to attend this course however pre-course reading of the pre-course handout is essential.
This a highly sought-after certification which indicates to employers an excellent understanding of the Six Sigma methodologies and how to effectively apply them to businesses. This course covers Yellow, Green and Black Belt content in one combined ten-day course.
Six Sigma Black Belts are known for having an astute business improvement acumen and the capability to take charge of a dynamic project team, assigning roles and responsibilities efficiently. Black Belts have a comprehensive knowledge of the DMAIC model in accordance with Six Sigma principles. By achieving a Six Sigma Black Belt certification from The Knowledge Academy, candidates will gain the leadership skills to be able to manage and lead quality improvement projects.
This course consists of 30 hours of pre-course work. This involves exercises on a number of pre-course guides. In addition, it is required for delegates to bring along a laptop that has up to date Minitab statistical computer software.
This course can be taken by individuals who have previously obtained the Six Sigma Green Belt certification and wish to upgrade their understanding to Black Belt level. Emphasis is placed upon training delegates to be outstanding leaders, capable of managing Six Sigma Green Belt teams that are working towards improving the quality of business processes.
Businesses that wish to carry out an improvement project require capable leaders to drive teams to success. When using a Six Sigma-based approach to quality improvement, organisations desire Black Belts to take on this challenging role. Six Sigma Black Belts have an astute business improvement acumen and the ability to assign roles and responsibilities efficiently and productively. Black Belts also possess a comprehensive knowledge of the DMAIC model in accordance with Six Sigma principles.
This Six Sigma course builds on what has previously been learned in the Green Belt course. Some pre-course reading, which will be supplied, should be carried out, and it is also required for delegates to bring along a laptop that has up to date Minitab statistical computer software.
Earning a Master Black Belt (MBB) certification indicates the highest level of understanding of Six Sigma. These individuals are imperative for determining the strategic direction of projects and overseeing the roles of Black and Green Belts.
Also, MBB's are responsible for acting as the organisation's Six Sigma internal consultant. MBB's possess exceptional leadership qualities and are committed to improving and advancing quality within a business. This fifteen-day training course is directed at individuals who have earned all previous certifications and therefore have an in depth understanding of the concepts of Six Sigma and a wealth of experience in applying them to industry.
There is approximately 2-3 hours of evening work required consisting of revision, research, and exercises. Delegates will be required to bring along a laptop that has up to date Minitab statistical computer software.


text:
BuyingApartment.com was founded in 2016 as the ultimate guide to buying your first apartment or condo.
The process, from deciding on your budget, to hiring a real estate agent, and finding your perfect apartment or condo can be complex and intimidating.
This website will help demystify some of the process, giving you a step-by-step guide so you can make an informed decision.


text:
The protective effects of nitric oxide (NO), a physiological activator of soluble guanylyl cyclase (sGC), have been reported in ischemia-reperfusion (I/R) syndrome of the lung. Therefore, we studied the effects of BAY 41-2272, a novel sGC stimulator, on I/R injury of the lung in an isolated intact organ model. Lung injury was assessed by measuring weight gain and microvascular permeability (capillary filtration coefficient, Kfc). Release of reactive oxygen species (ROS) into the perfusate was measured during early reperfusion by electron spin resonance (ESR) spectroscopy. Rabbit lungs were treated with BAY 41-2272, NG-monomethyl-l-arginine (l-NMMA), or NO to evaluate the effects on I/R-induced lung injury. In untreated lungs, a dramatic rise in Kfc values and weight gain during reperfusion were observed, and these results were associated with increased ROS production. Both, BAY 41-2272 and l-NMMA significantly attenuated vascular leakage and suppressed ROS release. Additional experiments showed that BAY 41-2272 diminished PMA-induced ROS production by NADPH oxidase. A pharmacological inhibition of the enzyme with consequent reduction in ROS levels decreased I/R injury. NO had only marginal effect on I/R injury. Thus BAY 41-2272 protects against I/R-induced lung injury by interfering with the activation of NADPH oxidases.
- acute lung injury
- nitric oxide
- oxidative stress
- reactive oxygen species
- guanosine 3′,5′-cyclic monophosphate
ischemia-reperfusion (I/R)-induced injury is defined as cellular damage that occurs after reperfusion of previously viable ischemic tissue. I/R injury may occur during organ transplantation, thrombendarterectomy, myocardial ischemia and revascularization, or stroke (8). The lack of effective therapeutic strategies to treat this disorder remains an issue.
An oxidative stress-induced damage is suggested to serve as a critical mechanism of I/R injury (36). Oxidative stress is characterized by the increased production of reactive oxygen species (ROS), such as superoxide radical, hydrogen peroxide, hydroxyl radical, and peroxynitrite. It has been shown that generation of ROS occurs during both ischemia and reperfusion (20, 35). The ability of SOD to attenuate I/R injury suggests that superoxide radical plays the crucial role in pathogenesis of this condition (25). Inhibition of NADPH oxidase, which is the major source of superoxide, has been reported to have a protective effect against vascular leakage in reperfused lungs (7).
The use of nitric oxide (NO) as a therapeutic tool for treating of I/R injury is an issue currently under debate (5). NO is an activator of intracellular soluble guanylyl cyclase (sGC), the activity of which increases the level of the second messenger cGMP. cGMP induces smooth muscle relaxation, reduces microvascular permeability, and inhibits neutrophil-endothelium interactions (18). It has not been elucidated whether NO confers protective or injurious effects. On one hand, exogenous administration of NO demonstrated protective effect in animal models of I/R (3) and in patients after lung transplantation (15), and it has been postulated that NO may protect by inhibition of neutrophil function (11). Other studies, however, have reported that NO inhalation can be detrimental to reperfused lungs (13, 32). Additionally, exogenous NO could bind with ROS to form peroxynitrite, which results in endothelial dysfunction (9).
A novel NO-independent sGC stimulator BAY 41-2272 was recently identified (31). BAY 41-2272 represents a new class of drugs that function by direct stimulation of sGC. This substance has a synergistic effect on stimulation of sGC when combined with NO (30). Stimulation of sGC by BAY 41-2272 may result in decreased I/R injury by restoring the cGMP signaling pathway. Therefore, the aim of our study was to clarify the effect of NO-independent stimulation of sGC on lung I/R injury.
Chemicals and Reagents
1-Hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) was purchased from Alexis (Lausen, Switzerland). Krebs-Henseleit buffer containing 120 mM NaCl, 4.3 mM KCl, 1.1 mM KH2PO4, 24 mM NaHCO3, 2.4 mM CaCl2, 1.3 mM MgCl2, and 13.32 mM glucose as well as 5% (wt/vol) hydroxyethylamylopectin (200,000 Da) was provided from Serag-Wiessner (Naila, Germany). The perfusate for ROS measurements containing the same salts in the same concentration was composed in situ and treated with Chelex (Bio-Rad, Hercules, CA) to remove trace amounts of Fe and Cu.
All animal experiments were approved by the local authorities. Male New Zealand White rabbits (body wt 2.8–3.5 kg) were used for all experiments. Animals were kept under pathogen-free conditions and handled in accordance with the European Communities recommendations for experimentation.
Isolated Lung Model
The technique of isolated rabbit lung perfusion has been described (26). Briefly, rabbits were anti-coagulated with 1,000 U/kg heparin and deeply anesthetized with ketamine and xylazine. Lungs were removed from the thorax without interruption of perfusion and ventilation and subsequently subjected to a recirculating system. Lungs were perfused with 100 ml/min Krebs-Henseleit buffer and ventilated with a gas mixture comprised of 5.3% CO2, 21% O2, 73.7% N2 (Messer, Siegen, Germany). A tidal volume of 30 ml, 30 breaths/min, and 1 cmH2O positive end-expiratory pressure (PEEP) using a Harvard respirator were used (cat/rabbit ventilator; Hugo Sachs Elektronik, March-Hugstetten, Germany). Left atrial pressure was set at 2 mmHg (referenced at the hilum), and the whole system was equilibrated at 39°C.
Pressures in the pulmonary artery and the left atrium were registered with pressure transducers, and the data were transferred to a computer. The capillary filtration coefficient (Kfc) was determined gravimetrically from the slope of the lung weight gain curve induced by a 7.5-mmHg step elevation of the venous pressure for 8 min as previously described (27). Lung weight gain was calculated as the difference in organ weight measured directly before and 5 min after each of these pressure elevation maneuvers.
Experimental Protocols
After termination of the initial steady-state period and performance of a control hydrostatic challenge, ischemia was induced in the lungs by stopping the perfusion and ventilation with anoxic gas mixture 5.3% CO2-94.7% N2 (Messer). To maintain positive intravascular pressure, the arterial and venous catheters were clamped after adjustment of initial value of arterial pressure to 6 mmHg. During ischemia, lungs were continuously ventilated with the warmed and humidified anoxic gas mixture. At the end of ischemia, ventilation was changed to normoxia, and perfusion was reestablished by increasing the flow from 0 to 100 ml/min stepwise over 3 min. Hydrostatic challenges were performed 30 and 60 min after the onset of reperfusion. Duration of the ischemic period and timings of hydrostatic challenges were designed based on our previous studies (17, 23, 24, 26).
Lungs were treated according to one of the following protocols. NIC: nonischemic control; lungs were perfused and ventilated throughout 7 h.
I/R: lungs were exposed to anoxic ischemia (applies to all of the following I/R groups) followed by reperfusion; no interventions were performed. BAY 41-2272: the substance (3 μM) was added to perfusion buffer 5 min before onset of ischemia. This dosage was determined to be the most effective based on previous dose ranging experiments (data not given in detail).
NG-monomethyl-l-arginine (l-NMMA): the nitric oxide synthase (NOS) blocker (400 μM) was added to the perfusion buffer 7 min before ischemia. BAY 41-2272 + l-NMMA: the substances were administered 5 and 7 min, respectively, before ischemia in the same concentrations as in the BAY 41-2272 and l-NMMA groups.
NO: NO (50 ppm) was added to ventilating gas mixture 1 min before reperfusion; NO inhalation was continued until the end of experiment. BAY 41-2272 + NO: the substances were used as described for the individual groups above.
Apocynin: apocynin (1 mM) was added to the perfusion buffer 5 min before onset of ischemia. SOD: 150 U/ml SOD was added to perfusion buffer 5 min before onset of ischemia.
Experiments were terminated if weight gain reached more than 25 g during reperfusion or at 60 min after reperfusion. Measurements of ROS release into perfusate were performed in additional experiments using the same protocol.
PMA Stimulation Experiments
Lungs were prepared as described above. After the initial steady-state period, CPH (1 mM) was added to the circulating buffer. Five minutes later, one of three different protocols was initiated:
One-hour perfusion period followed by a bolus application of PMA (final concentration 1 μM) into the pulmonary artery. Every 5 min, samples from the venous outflow of the isolated lung were taken in 50-μl glass capillaries and measured by electron spin resonance (ESR) as described in ESR Measurements in Perfusate below. After PMA stimulation, measurements were performed every 2 min.
After 30 min of perfusion with 1 mM CPH, the BAY 41-2272 was applied, followed by PMA stimulation 30 min later. Measurements were performed as described for the PMA group.
3. SOD controls.
After the steady-state period, 150 U/ml SOD was added to the buffer, followed by administration of CPH (1 mM). Subsequent interventions were executed as described for PMA and BAY 41-2272 + PMA groups.
NO Inhalation
NO was added to the inspiration gas. NO concentration was controlled by a chemiluminescence detector (NOA Sievers 280; Sievers, Seeheim, Germany). The concentrations of O2 and CO2 were kept constant during inhalation of NO.
Measurement of cGMP Concentration
cGMP was determined in samples of pulmonary venous effluent before ischemia as well as 3, 30, and 60 min after the onset of reperfusion. The perfusate aliquots were immediately frozen in liquid nitrogen and stored at −20°C until measurements were taken. Samples were analyzed by radioimmunoassay (Beckman Coulter, Hamburg, Germany). Briefly, the assay is based on the competition between succinylated cGMP in the sample and an 125I-labeled tracer for binding to a polyclonal antibody coated onto the tubes. Measurements were carried out in duplicate, and samples were treated with perchloric acid to inhibit PDE activity and extract the cyclic nucleotide. The extracts were then succinylated and assayed. Radiation was detected in a gamma-counter (Cobra Auto-gamma; Packard, Zurich, Switzerland).
Measurement of Exhaled NO
Measurements were performed as described by Spriestersbach et al. (29). Briefly, aliquots of exhaled gas were provided continuously for measurement by chemiluminescence technique to NOA Sievers 280.
Measurement of NO Concentration in Perfusate
NO metabolites (nitrite and nitrate) were determined in perfusate samples by NOA Sievers 280 according to manufacturer's instructions. Briefly, perfusate probes were sampled from venous effluent before ischemia as well as 3, 30, and 60 min after the onset of reperfusion and frozen immediately and stored under −20°C until measurements were taken. NO reaction products in samples were reduced by vanadium chloride. Resulting gaseous NO was detected by NOA Sievers 280, which was connected to a computer for data transfer and analysis by "NoaWin 32" software (DeMeTec, Langgöns, Germany).
ESR Measurements in Perfusate
The triple-line spectrum of CP· radical, a product of the reaction between spin probe CPH and ROS, was detected by ESR spectroscopy using a MS 100 spectrometer (Magnettech, Berlin, Germany). ESR measurements were performed in field scan with the following settings: microwave frequency 9.78 GHz, modulation frequency 100 kHz, modulation amplitude 2 G, and microwave power 18 mW (34). Spin probe 1 mM CPH was administered 5 min before reperfusion into the perfusate. Samples from the venous outflow of the isolated lung were taken immediately after the start of reperfusion in 50-μl glass capillaries and measured at room temperature. To decrease autooxidation of CPH due to iron, present in perfusate, 50 μM diethylenetriamine pentaacetic acid (DTPA) was applied before CPH.
NADPH Oxidase Activity Assay
Assay was performed as described previously (19). Briefly, 10% (wt/vol) tissue homogenate was prepared in 50 mM phosphate buffer (pH 7.4) containing 1 mM sodium vanadate, Complete protease inhibitor mix (Roche, Mannheim, Germany), and 0.1 mM PMSF. After lysis, homogenates were centrifuged at 20,000 g for 20 min at 4°C to pellet organelles. The supernatant was subjected to 100,000 g for 60 min at 4°C. Pellets, containing plasma membranes and microsomes, were resuspended and used for following analysis. Protein concentration was determined by Bradford assay (Bio-Rad, Munich, Germany). For determination of NADPH oxidase activity, 20 μg of protein were incubated with 1 mM NADPH, 1 mM CPH, and 50 μM DTPA in Chelex-treated PBS (pH 7.4) at 37°C for 30 min. From serial measurements by ESR spectroscopy, rate of ROS production was determined. To calculate rate of superoxide production, parallel reactions in presence of 100 U/ml SOD were performed, for which results are subtracted from values of each sample. Measurements were done using MS 100 spectrometer with settings as described above.
Data Analysis
Data are expressed as means ± SE. Differences between two groups were analyzed by t-test. For multiple comparisons, one-way analysis of variance followed by a post hoc Student-Newman-Keuls test was used. P values <0.05 were considered to represent a significant difference. Statistical analyses were performed using SPSS statistical software.
BAY 41-2272 Attenuates I/R-Induced Lung Injury
In the preischemic period, low Kfc values (1.13e−04 ± 0.15e−04 cm3 × s−1 × mmHg × g) indicated intact endothelial barrier properties in all experimental groups. After 4-h ischemic exposure, control lungs displayed dramatically elevated Kfc values (Fig. 1) on reperfusion (Kfc: 13.2e−04 ± 1.80e−04 cm3 × s−1 × mmHg × g) with subsequent severe edema formation. Pretreatment with BAY 41-2272 significantly attenuated vascular leakage and reduced edema (Kfc: 4.39e−04 ± 0.51e−04 cm3 × s−1 × mmHg × g; P < 0.01). Interestingly, complete blockage of NOS activity with l-NMMA also protected against I/R injury (Kfc: 6.00e−04 ± 1.80e−04; P < 0.05). The combination of BAY 41-2272 and l-NMMA had additive protective effect on the microvascular leakage response (Kfc: 3.08e−04 ± 0.71e−04; P < 0.01 vs. I/R). Organ protection with inhaled NO was not as potent as with BAY 41-2272 (Figs. 1 and 2). Coadministration of BAY 41-2272 and inhaled NO resulted in partial loss of organ protection compared with the effect of BAY 41-2272 alone. Changes in weight gain correlated well with changes in Kfc values (Fig. 2).
Pulmonary arterial pressure.
Average pulmonary arterial pressure (Ppa) was determined to be 6.76 ± 0.23 mmHg during the preischemic period with no significant differences observed between groups. BAY 41-2272 application caused a slight decrease in basal vascular tone. Inhibition of NO formation by l-NMMA did not significantly affect the baseline pulmonary vascular tone. Reperfusion in I/R group caused a transient Ppa increase (16.28 ± 2.14 mmHg) followed by decrease to the baseline level. BAY 41-2272 significantly attenuated Ppa rise after reperfusion (7.63 ± 0.54 mmHg; P < 0.01 vs. I/R; Fig. 2). l-NMMA did not significantly affect Ppa increase (15.51 ± 2.46 mmHg). Combined application of BAY 41-2272 and l-NMMA was less efficient at decreasing transient Ppa rise than BAY 41-2272 alone (12.52 ± 1.21 mmHg). Inhaled NO alone and in combination with BAY 41-2272 did not significantly influence the transient Ppa increase.
Exhaled NO and NO metabolites in the perfusate.
NO release detected in the exhaled gas mixture (NOex) was 75.33 ± 5.52 ppb under preischemic control conditions. On initiation of ischemia, NOex decreased immediately and remained low during the entire ischemic period (1.33 ± 1.09 ppb shortly before reperfusion). After the onset of reperfusion, levels of NOex returned to baseline levels (Fig. 3A). NO metabolites in perfusate accumulated continuously in the course of experiment. BAY 41-2272 did not significantly influence NOex and NO metabolites in perfusate. l-NMMA-mediated inhibition of NOS was confirmed by a rapid drop of NOex and diminished accumulation of NO metabolites after l-NMMA application. Moreover, l-NMMA blocked the recovery of NO production after reperfusion (23.8 ± 1.97 ppb; P < 0.001 vs. I/R). These effects of l-NMMA were also observed on combined application of BAY 41-2272 and l-NMMA. As expected, addition of NO to the inspired gas mixture resulted in a significant increase of NOex and NO metabolites, which masked any changes in endogenous NO production.
Concentration of cGMP in perfusate.
The concentration of cGMP for I/R group in the perfusate was 0.32 ± 0.07 nM at baseline and was the same for all groups (Fig. 4). The concentration of cGMP slightly increased during the observation period (2.75 ± 0.32 nM). The cGMP concentration significantly increased in the groups treated with BAY 41-2272 and exogenous NO (39.93 ± 0.85 and 29.50 ± 5.39 nM; P < 0.001 and P < 0.01 vs. I/R control, respectively), whereas l-NMMA inhibited increases in cGMP concentrations. Interestingly, combined application of l-NMMA and BAY 41-2272 resulted in elevated cGMP levels but to a lesser extent than that induced by BAY 41-2272 alone (17.30 ± 0.85 nM; P < 0.01, BAY 41-2272 + l-NMMA vs. BAY 41-2272). Most likely, this reveals the NO-independent part of the sGC stimulatory effect of BAY 41-2272. The combination of BAY 41-2272 with inhaled NO induced enormous increase of the cGMP levels (154.13 ± 42.82 nM; P < 0.01 vs. NO). On the other hand, this dramatic rise was not paralleled by a significant improvement of I/R-induced permeability disturbances (Fig. 1).
BAY 41-2272 Reduces I/R-Induced ROS Release in Perfusate
In lungs exposed to ischemia, a significant increase in ROS release in the perfusate on onset of reperfusion was detected, whereas the NIC lungs showed no significant increase (Fig. 5). Application of SOD reduced significantly CP· signal suggesting that the superoxide is the predominant radical produced. BAY 41-2272 as well as l-NMMA diminished ROS release. However, the combination of BAY 41-2272 and l-NMMA did not further decrease the ROS levels in the perfusate. Inhaled NO and the combination of exogenous NO and BAY 41-2272 failed to reduce ROS release in perfusate.
BAY 41-2272 Inhibits I/R and PMA-Induced NADPH Oxidase Activation
NADPH oxidase activity was inhibited in the BAY 41-2272-treated lungs as demonstrated in Fig. 6.
During steady-state period, the lungs in PMA group demonstrated stable Ppa (8.63 ± 0.34 mmHg) with no significant differences between groups. PMA stimulation resulted in increased ROS release in the perfusate of isolated lungs, which was accompanied by a pronounced increase in Ppa (Fig. 7). BAY 41-2272 significantly inhibited an increase in both ROS production (Fig. 7A) and Ppa elevation (Fig. 7B). SOD completely suppressed superoxide release accompanied by a reduced pressure response.
NADPH Oxidase is Involved in Mediation of I/R Injury
Application of the NADPH oxidase inhibitor apocynin protected against I/R-induced injury (Fig. 8). Apocynin protected against increase in permeability and reduced weight gain (14.4 ± 2.34 g; P < 0.05 vs. I/R; Fig. 8, A and B). Additionally, apocynin reduced reperfusion-induced Ppa increase (Fig. 8C). NADPH oxidase inhibition was confirmed via decreased ROS release in perfusate in apocynin-treated lungs (Fig. 8D).
The main findings of this study are: 1) direct stimulation of sGC by BAY 41-2272 protects against I/R lung injury; 2) this protective effect is not modulated by NO; and 3) stimulation of sGC leads to inhibition of NADPH oxidase.
Direct stimulation of sGC by BAY 41-2272 potently prevented an increase in vascular permeability and fluid retention in the BAY 41-2272-treated lungs. Interestingly, BAY 41-2272 inhibited the observed increase in ROS release into perfusate after reperfusion. One of the features of I/R injury is a transient pressure increase after reperfusion. Direct stimulation of sGC by BAY 41-2272 inhibited this increase. Whether the hydrostatic challenge of increased pressure (4, 28) or the permeability disturbance as result of oxidative stress (36) is a driving force of I/R-induced lung injury remains under debate. Hence, BAY 41-2272 seems to influence both possible components that drive lung injury.
BAY 41-2272 has been described as a highly potent and specific NO-independent stimulator of sGC (1), which has an additive effect when combined with NO (30). Therefore, we tested the effect of BAY 41-2272 and inhalative NO coadministration on I/R lung injury. The combination of BAY 41-2272 and NO caused significant increase in cGMP concentration in the perfusate. However, this combination resulted in a loss of protective effect on I/R injury compared with BAY 41-2272 alone. This observation could be partially explained by the adverse effect of peroxynitrite, which is produced from NO in an oxidizing environment.
Although the most effective dose and regimen of NO inhalation were chosen based on comparison of different approaches of NO application (21), inhalation of NO was less efficient to reduce increased permeability compared with BAY 41-2272. Interestingly, increase in cGMP concentration in the perfusate was comparable between groups treated with BAY 41-2272 and NO inhalation, which suggests that both agents had comparable potency in sGC stimulation. In the NO treatment group, ROS release into perfusate was not significantly different from that in the I/R group. Superoxide, which is produced after reperfusion, reacts with NO to form peroxynitrite. Thus increased peroxynitrite formation in NO-treated group cannot be excluded as a possible ROS released into perfusate, and this could overwhelm positive effects of NO. Indeed, these results are in accordance with the findings of other studies (13), where deleterious effect of exogenous NO (20–30 ppm) on I/R-induced rat lung injury has been demonstrated.
I/R has been shown to lead to upregulation of inducible NOS (iNOS) expression, resulting in increased amounts of endogenous NO (16). Excessive activation of iNOS can lead to the depletion of NOS cofactors such as tetrahydrobiopterin (14). This, in turn, could lead to uncoupling of endothelial NOS (eNOS) and switch from NO synthesis to superoxide production (9). Thus blockade of NOS might be another approach to reduce oxidative stress and prevent lung injury.
Indeed, in the present study, we observed that l-NMMA has a positive effect on the reduction of I/R-induced lung injury. Complete blockade of NO production by both iNOS and eNOS was achieved as evidenced by very low levels of exhaled NO and cGMP levels in perfusate. This was associated with significant reduction in ROS release in perfusate in the early reperfusion period. Inhibition of the ROS production may be due to prevention of ROS formation by uncoupled NOS. Similar results were observed in another study where treatment with l-NMMA reduced ROS production in the early reperfusion (2).
The combination of BAY 41-2272 and l-NMMA resulted in further reduction of I/R-induced injury. We suggest that l-NMMA and BAY 41-2272, despite having opposite effects on NO-cGMP signaling pathway, have additive effect in this situation because they inhibit two different components involved in the mediation of ROS-induced injury. l-NMMA inhibits uncoupled NO synthases, thereby preventing superoxide production, whereas BAY 41-2272 restores the NO-cGMP signaling pathway, preventing activation of NADPH oxidase. This results in synergistic effect in protection of vascular permeability and weight gain changes.
We suggest that BAY 41-2272 decreases I/R injury by inhibiting NADPH oxidase-derived ROS production, as YC-1, a substance structurally related to BAY 41-2272, has been shown to inhibit formyl-Met-Leu-Phe (fMLP)-induced ROS production (12, 33). NO-cGMP signaling pathway has been shown to interfere with NADPH oxidase by inhibiting its assembly (10) and by inhibiting its expression (22). Indeed, we observed that BAY 41-2272 inhibited both the increase in ROS production and the Ppa increase induced by PMA, a stimulator of NADPH oxidase activity. Moreover, NADPH oxidase activity, as measured in the membrane fractions from lung homogenates, was reduced in the BAY 41-2272 treatment group. Activation of NADPH oxidase has been demonstrated to contribute to the development of I/R injury (7). Indeed, we found that in our experiments, inhibition of NADPH oxidase with apocynin protected against development of I/R lung injury. Thus activation of NADPH oxidase plays an important role in the mediation of I/R injury, and BAY 41-2272 exerts its effect, at least, in part, by preventing the activation of this enzyme.
Thus we conclude that both inhibition of NOS activity by l-NMMA and stimulation of sGC activity by BAY 41-2272 result in protective effects against I/R-induced lung injury. We observed only marginal effects of inhaled NO on I/R injury possibly due to increased peroxynitrite formation. We suggest that l-NMMA exerts its positive effect by preventing free radical formation catalyzed by uncoupled NO synthases and BAY 41-2272 protects against I/R-induced injury by restoring the NO-cGMP signaling pathway and preventing NADPH oxidase activation.
Funding sources for this study were German Research Foundation [Deutsche Forschungsgesellschaft (DFG), SFB 547] and Excellence Cluster Cardio-Pulmonary System (ECCPS).
Parts of the doctoral thesis of B. Egemnazarov are included in the manuscript. We thank K. Quanz for assistance in cGMP measurements.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2009 the American Physiological Society