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Kindergarten Reading List
Any Book by Martha Alexander I Sure Am Glad To See You, Blackboard Bear You're A Genius, Blackboard Bear Marty Mcgee's Space Lab, No Girls Allowed Move Over, Twerp We're In Big Trouble, Blackboard Bear My Outrageous Friend Charlie Nobody Asked Me If I Wanted A Baby Sister When The New Baby comes, I'm Moving Out And My Mean Old Mother Will Be Sorry, Blackboard Bear How My Library Grew, by Dinah
Any Book by Kathi Applet Alley Cat's Meow Bat Jamboree Bats Around The Clock Bayou Lullaby Best Kind Of Gift Bubba And Beau Best Friends Bubba And Beau Go Night-Night Bubba And Beau Meet The Relatives Incredible Me Merry Christmas, Merry Crow Oh My Baby, Little One Piggies In A Polka Watermelon Day Where, Where Is Swamp Bear?
Any Beginning Reader by Crosby Bonsall And I Mean It, Stanley The Case Of The Dumb Bells The Case Of The Hungry Stranger The Case Of The Scaredy Cats The Case of the Cat's Meow Mine's The Best Piggle: A Homer Story Tell Me Some More Twelve Bells For Santa Who's Afraid Of The Dark?
Little Badger's Just-About Birthday Little Badger, Terror Of The Seven Seas and Can You Do This, Old Badger? by Eve Bunting
Any Book by Eric Carle Do You Want To Be My Friend? Does A Kangaroo Have A Mother, Too? Draw Me A Star Dream Snow From Head To Toe The Grouchy Ladybug Hello, Red Fox A House For Hermit Crab Little Cloud Mister Seahorse The Mixed-Up Chameleon Pancakes, Pancakes! Papa, Please Get The Moon For Me Today Is Monday "Slowly, Slowly, Slowly," Said The Sloth The Secret Birthday Message 10 Little Rubber Ducks The Very Busy Spider The Very Clumsy Click Beetle The Very Hungry Caterpillar The Very Lonely Firefly The Very Quiet Cricket Rooster 's Off To See The World Dragons Dragons & Other Creatures That Never Were
Giggle Giggle Quack and Click Clack Moo by Doreen Cronin
Any Picture Book by Dr. Seuss The 500 Hats Of Bartholomew Cubbins Bartholomew And The Oobleck Daisy-Head Mayzie The Butter Battle Book Gerald Mcboing Boing Happy Birthday To You! Hooray For Diffendoofer Day! Horton Hatches The Egg Horton Hears A Who! How The Grinch Stole Christmas Hunches In Bunches I Can Lick 30 Tigers Today The King's Stilts I Had Trouble In Getting To Solla Sollew The Lorax McElligot's Pool My Many Colored Days Oh, The Places You'll Go! Oh, The Thinks You Can Think! On Beyond Zebra Scrambled Eggs Super! The Sneetches, And Other Stories Thidwick, The Big-Hearted Moose And To Think That I Saw It On Mulberry Street Any Easy Reader by Dr. Seuss The Cat in the Hat The Cat in the Hat Comes Back The Foot Book Fox in Socks Great Day for Up! Green Eggs and Ham Hop on Pop I Am Not Going To Get Up Today Horton Hears A Who! I Can Read With My Eyes Shut I Wish That I Had Duck Feet Oh Say Can You Say? There's a Wocket in My Pocket Marvin K. Mooney, Will You Please Go Now! One Fish, Two Fish, Red Fish, Blue Fish Ten Apples Up On Top
Gossie and Gossie & Gertie by Olivier Dunrea
Are You My Mother? Go, Dog, Go and Sam and the Firefly by P.D. Eastman
Any Book by Lois Ehlert Color Farm Color Zoo Growing Vegetable Soup Mole's Hill Oodles of Animals Feathers For Lunch! Fish Eyes:A Book You Can Count On Nuts To You! Red Leaf Yellow Leaf Snowballs Top Cat Waiting For Wings Pie In The Sky Planting A Rainbow Leaf Man Eating The Alphabet
Corduroy by Don Freeman
Let's Get A Pup by Bob Graham
You Read To Me, I'll Read To You (series) by Mary Ann Hoberman
Any Book by Robert Kraus Big Squeak, Little Squeak Come Out And Play Little Mouse Leo The Late Bloomer Musical Max Near Myths: Dug Up And Dusted Off Noel The Coward Sturdwick: A Sheep In Wolf's Clothing Mort The Sport Where Are You Going Little Mouse? Whose Mouse Are You?
That Makes Me Mad by Steven Kroll
Water Hole Waiting by Jane Kurtz
Clarence The Copy Cat by Pat Lakin
Any Book by Mercer Mayer Appelard And Liverwurst A Boy, A Dog, And A Frog A Boy, A Dog, A Frog, And A Friend Frog Goes To Dinner Frog On His Own Hiccup There's A Nightmare In My Closet There Are Monsters Everywhere There's An Alligator Under My Bed There's Something In My Attic Just A Snowman Good For Me And You I Was So Mad Just Me And My Babysitter Just Me And My Mom This Is My Town Snowball Soup Skating Day Little Critter At Scout Camp A Day At Camp When I Get Bigger
Hondo & Fabian by Peter McCarty
Any Counting Book by Jerry Pallotta The Crayon Counting Book Reese's Pieces: Count By Fives Underwater Counting: Even Numbers Icky Bug Counting Book Twizzlers Percentages Book The Hershey's Kisses Addition Book The Hershey's Kisses Subtraction Book The Hershey's Milk Chocolate Multiplication Book The Hershey's Milk Chocolate Bar Fractions Book
The Broken Cat by Lynne Rae Perkins
Little Flower by Gloria Rand
100 School Days by Anne Rockwell
My Friend Rabbit by Eric Rohmann
Big Bear Ball by Joanne Ryder
The Great Gracie Chase by Cynthia Rylant
All You Need For A Snowman by Alice Schertle
Hidden Alphabet by Laura Seeger
Duck On A Bike &by David Shannon
Quiet Night by Marilyn Singer
B Is For Bulldozer by Jane Sobel
Madlenka and Madlenka's Dog by Peter Sis
Any Book by William Steig The Amazing Bone Amos & Boris Brave Irene C D B! C D C? Caleb & Kate Doctor De Soto Doctor De Soto Goes To Africa Pete's A Pizza Shrek! Spinky Sulks Sylvester And The Magic Pebble Toby, What Are You? Toby, Where Are You? The Toy Brother Which Would You Rather Be? Wizzil Zeke Pippin Alpha Beta Chowder
Get Well, Good Knight by Shelley Moore Thomas
Any Book by Bernard Waber An Anteater Named Arthur Bearsie Bear And The Surprise Sleepover Party But Names Will Never Hurt Me Courage Do You See A Mouse? Funny, Funny Lyle Gina Good-Bye, Funny Dumpy-Lumpy The House On East 88th Street Ira Says Goodbye Ira Sleeps Over A Lion Named Shirley Williamson Lovable Lyle Lyle And The Birthday Party Lyle At The Office Lyle Finds His Mother Lyle, Lyle, Crocodile Fast Food! Gulp! Gulp! The Mouse That Snored Evie & Margie ''You Look Ridiculous,'' Said The Rhinoceros To The Hippopotamus
Any Book by Rosemary Wells Bunny Cakes Bunny Money Bunny Party Discover And Explore Edward In Deep Water Edward Unready For School Edward's Overwhelming Overnight Emily's First 100 Days Of School Felix Feels Better Felix And The Worrier Only You First Tomato Forest Of Dreams Fritz And The Mess Fairy The House In The Mail How Many? How Much? The Island Light The Language Of Doves Letters And Sounds Lucy Comes To Stay Max And Ruby's First Greek Myth Max And Ruby's Midas: Another Greek Myth Max Cleans Up Max's Bunny Business Max's Counts His Chickens Max's Dragon Shirt McDuff And The Baby McDuff Comes Home McDuff Goes To School McDuff Moves In McDuff Saves The Day Moss Pillows My Kindergarten Night Sounds, Morning Colors Noisy Nora Ready To Read: Based On Timothy Goes To School Ruby's Beauty Shop Shy Charles The Small World of Binky Braverman Stanley & Rhoda Timothy Goes To School Timothy's Tales From Hilltop School Waiting For The Evening Star The World Around Us Yoko Yoko's Paper Cranes
Whatever Wanda Wanted by Jude Wisdom
Bear Snores On by Karma Wilson
How Do Dinosaurs Get Well Soon by Jane Yolen


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Ford Escape Pioneer Car Stereo Install
The owner of this 2006 Ford Escape wanted to get a new Pioneer car stereo installed so he could have all the latest technology. To get the new Pioneer touch screen stereo to fit nicely we used Metra's double din installation dash kit number 95-5812. We used a factory amp integration harness number 70-5522. Since the customer wanted to keep his steering wheel controls functional we installed the ASWC-1. To add satellite radio to the Pioneer deck we used the SXV300V1. He now has quality hands free calling, an easy to use touch screen, and satellite radio. This clean looking Ford Escape Pioneer car stereo install was done by the pros at Quality Auto Sound 586 S. Chambers Rd. Aurora, CO 80017 303-695-1500. Your local car audio specialist.

subset: commoncrawl


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HDS Carbon
The Carbon HDS Series combines side imaging, downscan imaging, dual-channel CHIRP sonar, real-time underwater 3D mapping capabilities and ultra-bright displays to deliver the most advanced and easy-to-use fish finder/chart plotter on the market. The units' touch-screen interface works much like a smartphone with pinch-to-zoom and touch-and-move abilities for fast and intuitive control.
HDS Carbon units also feature the ability to create custom maps using recorded sonar logs. Anglers can add custom color layers, vegetation and bottom-hardness overlays. Each unit supports the most advanced marine technology and is easily updated to the most current software for optimal performance.


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Please ensure that pop-up blockers are disabled in order to proceed.
Date: May 22, 2019
Location: FRAMINGHAM, MA, US, 01701
About CenturyLink
CenturyLink (NYSE: CTL) is the second largest U.S. communications provider to global enterprise customers. With customers in more than 60 countries and an intense focus on the customer experience, CenturyLink strives to be the world's best networking company by solving customers' increased demand for reliable and secure connections. The company also serves as its customers' trusted partner, helping them manage increased network and IT complexity and providing managed network and cyber security solutions that help protect their business.
Job Summary
In this role, you will work with seasoned engineers who are creating new products and services using leading-edge NFV and SDN technology. As a key member of the team you will be working in a fast-paced agile environment and contributing to all phases of the software development lifecycle from concept and design to testing.
Job Description
The candidate will be working within an Agile development team and will be responsible for development of routing, switching and related Operating System services. Development will combine multiple open source and third party software implementations as well as internal implementation.
The candidate must have excellent problem solving and communication skills, and must be self-motivated. The work will include:
- C language coding at expert level
- Python language coding at advanced level
- Implementation of new features and bug fixing for CenturyLink switching and routing platforms
- New features and bug fixing in the areas of:
- Routing and Switching protocols (such as BGP, OSPF, ISIS, STP, LDP, PIM, RSVP-TE)
- Internal control plane communication protocols (such as OpenFlow, OVSDB, WS APIs)
- Linux OS
- Software Packet forwarding using DPDK
- Managemement protocols and internal APIs for management
- system platform support software
- Minimum of 5 years experience with routing and switching development
- Minimum 5 years experience with development in a Linux environment required
- Expert C language skills required
- Advanced Python language skills required
- Knowledge and understanding of packet forwarding technology inluding Linux kernel, DPDK, OVS desirable
- Knowledge and understanding of network concepts including IP, Ethernet required
- Experience with NFV development desirable
- Development experience with management protocols and models including Yang, Netconf, ReST desirable
- Strong problem solving and communication skills required
Bachelors or Equivalent
Masters or Equivalent
Alternate Location: US-Massachusetts-Framingham
Requisition #: 204999
This job may require successful completion of an online assessment. A brief description of the assessments can be viewed on our website at http://find.centurylink.jobs/testguides/
EEO Statement
We are committed to providing equal employment opportunities to all persons regardless of race, color, ancestry, citizenship, national origin, religion, veteran status, disability, genetic characteristic or information, age, gender, sexual orientation, gender identity, marital status, family status, pregnancy, or other legally protected status (collectively, "protected statuses"). We do not tolerate unlawful discrimination in any employment decisions, including recruiting, hiring, compensation, promotion, benefits, discipline, termination, job assignments or training.
The above job definition information has been designed to indicate the general nature and level of work performed by employees within this classification. It is not designed to contain or be interpreted as a comprehensive inventory of all duties, responsibilities, and qualifications required of employees assigned to this job. Job duties and responsibilities are subject to change based on changing business needs and conditions.
Nearest Major Market: Framingham
Nearest Secondary Market: Boston
Job Segment: Developer, Software Engineer, Systems Engineer, Engineer, Cloud, Technology, Engineering
Please ensure that pop-up blockers are disabled in order to proceed.
Working at CenturyLink
Join our team and become part of a group that strives to learn, grow, and connect every day.


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Mission and Vision
Jump-Start Performance Co.'s Arts Education Program builds long-term collaborations with schools, organizations, youth, and other community members. We believe that teaching multi- disciplinary arts techniques and critical thinking skills nurtures mutual respect and individual creativity to effect dynamic change in our community.
Art is a powerful tool for empowering individuals to discover constructive ways to make their voices heard, to impact their communities, and to take control of their future. Through the arts, individuals can hone higher-level thinking skills, explore group processes, problem-solve for the future, develop creative potential and self-esteem, learn multidisciplinary processes (using various arts disciplines), and enhance cognitive development. In its educational work, Jump- Start plays a pioneering role in creating programs that focus on long-term collaboration and integrating the arts with social issues and academic achievement.


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Today's Sweet6 NYC Events>SATURDAY/FEB.11, 2017
"We search the internet everyday looking for the very best of What's Happening, primarily on Manhattan's WestSide, so that you don't have to." We make it as easy as 1-2-3.
For future NYC Events be sure to check the tab above: "Notable NYC Events-Feb."
Have time for only one NYC Event today? Do this:
Dianne Reeves
Rose Theater, Jazz @ Lincoln Center,/ 8PM, $31+
Singer Dianne Reeves has covered the stylistic waterfront over the years, but mostly she's an ace at singing standards. This will be her sixth year performing a Valentine's special at the Rose Theater, one of the city's most breathtaking concert venues, and it's sure to be heavenly." (TONY)
"Dianne Reeves will assuredly set the mood for this beloved Jazz at Lincoln Center tradition as she returns for the sixth time to seduce audiences with songs and stories of love and romance. Her alluring sound, fondness of love songs, and unusually broad spectrum of sensual repertoire promises a special Valentine's Day weekend performance. With nuanced restraint and dynamics, Reeves inhabits every story she spins into song. The fifteen-time Grammy® Award winner has long revered New York City and often chooses to spend her Valentine's Day in this shimmering city of romance."
5 OTHER TOP NYC EVENTS TODAY (see below for full listing)
The Losers Lounge Tribute to Philadelphia Soul:
The 70s Soul Jam Valentine's Concert
Joe Farnsworth and Kenny Washington
Centre Choreographique National—Ballet de Lorraine
Patti LaBelle
You saw these here recently and they continue today:
New York City Ballet – The Sleeping Beauty
Music, Dance, Performing Art
The Losers Lounge Tribute to Philadelphia Soul:
The Music of Gamble, Huff and Bell featuring the Songs of The O'Jays, The Delfonics, The Spinners, The Stylistics and more…
Joe's Pub / 7:00PM, +9:30PM, $25
"In the mid-1970s record producers Kenny Gamble, Leon Huff and Thom Bell created a new world of pop-music hailing from The City of Brotherly Love, called "Philadelphia Soul." Joe McGinty – The Losers Lounge Band Leader – says, "The 'Philadelphia Soul' sound combined sophisticated arrangements a la Burt Bacharach with soulful grooves a la Motown to create an incredible string of hits by groups like the O'Jays, The Spinners, The Delfonics, and The Stylistics. Having grown up in South Jersey, the Philadelphia Soul sound has always been a huge influence to me." Sexy, funky, danceable and lush, the arrangements of The Philadelphia Soul sound are credited with being the precursor to Disco as well as an influence on pop music at large to this day."
The 70s Soul Jam Valentine's Concert
Beacon Theater, / 3PM, +8PM, $49-$79
"Share the love at the 70s Soul Jam Valentine's Concert featuring legendary R&B/ soul groups The Stylistics, The Dramatics, The Delfonics, The Manhattans, and Blue Magic on Saturday, February 11 at NYC's landmark Beacon Theatre, with shows at 3pm and 8pm.
During the early '70s, The Stylistics were the leading Philly soul group with 12 straight Top Ten hits, including "You Are Everything" "Betcha by Golly, Wow" "I'm Stone in Love With You" "Break Up to Make Up" and "You Make Me Feel Brand New." Of all their peers, The Stylistics were one of the smoothest and sweetest soul groups of their era."
Joe Farnsworth and Kenny Washington (thru Feb.12)
Smoke Jazz Club, 2751 Broadway, btw 105th/106th Sts./ 7, 9, 10:30PM, $38
"There's always been a gladiatorial aspect to jazz. For an extra emphasis on blood sport, head uptown for this mano-a-mano fight to the finish between two supremely accomplished drummers with a mutual taste for hard-bop intensity. Urging on the contestants will be such familiar cohorts as Eric Alexander, on tenor saxophone; Steve Davis, on trombone; and Peter Washington—Kenny's unrelated bandmate in the Bill Charlap trio—on bass." (NewYorker)
Centre Choreographique National—Ballet de Lorraine (also Feb. 12 – 2 p.m)
Joyce Theater / 2PM, +8PM, $36+
"The contemporary dance company, a laboratory for new work based in Amiens, in northern France, makes its first visit to New York. Particularly interesting is "Sounddance" (on Program A), a furiously paced Merce Cunningham work from 1975 in which the dancers enter and exit the stage through a weird tentlike structure. Program B consists of a single evening-length dance cobbled together from the efforts of five choreographers whose identities are kept intentionally hidden, allowing the audience to experience the dance without preconceptions." (NewYorker)
Elsewhere, but this sure looks worth the detour:
Patti LaBelle
Kings Theatre, 1027 Flatbush Ave. Brooklyn / 8PM, $85+
"Patti Labelle, the versatile two-time Grammy Award winning singer and songwriter is certainly no stranger to most. The soulful songbird's name has become synonymous with grace, style, elegance, and class. Belting out classic rhythm and blues renditions, she has received acclaim for hits like "On my Own," "Lady Marmalade," "If Only you Knew, "Hear my Cry" and many more. Treat you sweetheart, family or friend to a wonderful Valentine's gift with the Godmother of Soul."
Smart Stuff / Other NYC Events
(Lectures, Discussions, Book Talks, Literary Readings, Classes, Food & Drink, Other)
more select events coming soon.
Bonus NYC events– Jazz Venues:
Many consider NYCity the Jazz capital of the world. Here are my favorite Jazz clubs, all on Manhattan's WestSide. Check out who is playing tonight:
Greenwich Village (all six are within walking distance of each other):
Village Vanguard – 178 7th Ave. South, villagevanguard.com, 212-255-4037
Blue Note – 131 W3rd St. nr 6th ave. bluenotejazz.com, 212-475-8592
55 Bar – basement @55 Christopher St. nr 7th ave.S. 55bar.com, 212-929-9883
Mezzrow – basement @ 163 W10th St. nr 7th Ave. mezzrow.com,646-476-4346
Smalls – basement @ 183 W10th St. smallslive.com, 646-476-4346
Cornelia Street Cafe – 29 Cornelia St. corneliastreetcafe.com, 212-989-9319
Outside Greenwich Village:
Dizzy's Club – Broadway @ 60th St. — jazz.org/dizzys / 212-258-9595
Birdland – 315 W44th St.(btw 8/9ave) — birdlandjazz.com / 212-581-3080
Smoke Jazz Club – 2751 Broadway nr.106th St. — smokejazz.com / 212-864-6662
Special Mention:
Caffe Vivaldi – 32 Jones St. nr Bleecker St. — caffevivaldi.com / 212-691-7538
a classic, old jazz club in the Village, Caffe V often surprises with a wonderfully eclectic lineup. It's my favorite spot for an evening of listening enjoyment and discovery.
♦ Before making final plans, we suggest you call the venue to confirm ticket availability, dates and times, as schedules are subject to change.
♦ NYCity, with a population of 8.5 million, had a record 60 million visitors last year and was TripAdvisor's Traveler's Choice Top U.S. Destination for 2017. Quality shows draw crowds.
Try to reserve seats for these top NYC events in advance, even if just on day of performance.
NYCity Vacation Travel Guide Video (Expedia):
Chelsea Art Gallery District*
Chelsea is the heart of the NYCity contemporary art scene. Home to more than 300 art galleries, the Rubin Museum, the Joyce Theater and The Kitchen performance spaces, there is no place like it anywhere in the world. Come here to browse free exhibitions by world-renowned artists and those unknowns waiting to be discovered in an art district that is concentrated between West 18th and West 27th Streets, and 10th and 11th Avenues. Afterwards stop in the Chelsea Market, stroll on the High Line, or rest up at one of the many cafes and bars and discuss the fine art.
Time Out New York highlights this current exhibition:
"Sergei Eisenstein: Drawings 1931–1948" (LAST DAY)
Alexander Gray Associates, 510 W26th St.
"Did you know that the director of Battleship Potemkin drew pornographic pictures in his downtime? Us neither, but as this roundup of his explicit exertions on paper clearly demonstrate, it's true. The show spans the period from 1931 until his death in 1948."
For a listing of 25 essential galleries in the Chelsea Art Gallery District, organized by street, which enables you to create your own Chelsea Art Gallery crawl, see the Chelsea Gallery Guide (nycgo.com) Or check out TONY magazine's list of the "Best Chelsea Galleries" and click through to see what's on view.
*Now plan your own gallery crawl, but better to plan your visits for Tuesday through Saturday; most galleries are closed Sunday and Monday.
TIP: After your gallery tour, stop in Ovest at 513W27th St. for Aperitivo Italiano (Happy Hour on steroids). Discuss all the great art you have viewed over a drink and a very tasty selection of FREE appetizers (M-F, 5-8pm).
For other selected Museum and Gallery Special Exhibitions see recent posts in right sidebar dated 02/09 and 02/07.


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Comfort Discovered has been in operation for over thirty years and have had a very large number of satisfied customers. Here are some of the more recent testimonials customers have voluntarily offered us.
"I bought an electric chair off this company and I was impressed with the genuineness of their interest in my welfare. I am very happy with the electric chair and can confirm that I am one of the only ones to have been put into an electric chair and survived to tell the tale.
I recommend Comfort Discovered because of their genuine interest in helping people."
"I'm a full-time carer of my grandmother. To be able to keep her home as she becomes more frail, we needed a range of mobility equipment. Reji and his team were great- they helped me decide what we did and didn't need (instead of just trying to sell us stuff). For example, when we were going to need an expensive version of a shower chair, Reji was apologetic about the price!
Also, my experience in most of aged care is that providers always seem to expect me to know everything. It's frustrating and isolating. Comfort Discovered take the time to get to know your circumstances and make appropriate recommendations - they ask questions instead of relying on you to know what you need (because what do I know about mobility equipment?). They are supportive, give you options, and actually care that you've got the right solutions for your circumstances. I can't recommend them highly enough." - KATHLEEN O'ROURKE
"Thank you to you all for coming to our aid in regard to the electric chair for my son. You all went out of your way to help us when we needed it."
"Comfort Discovered is a very friendly and helpful company offering a huge range of products to assist people in our community who are disabled or elderly. The staff is highly knowledgeable about the many modern solutions available to assist ..." - ADRIENNE MCLEAN
"I am a 78 year old paraplegic completely unable to use my legs to even stand up or walk and have been like this for 14 months. Initially I was recommended to a number of other suppliers by so called occupational therapists where I purchased the inappropriate wheelchairs [two] a shower chair and various small pieces of equipment which were inappropriate and have had to be discarded. I was recommended to Comfort Discovered by one of my Carer's. I have since replaced the two wheelchairs, modified the shower chair, purchased an adjustable "Hospital" bed with mattress and other comfort items eg. Padded socks, arm extensions, back scratchers to name just a few. All have been perfect for my needs and it has been well over $3000 well spent whereas on the wrong equipment I wasted over half this amount. It is so important to be guided by proven experts and Rejimon and Geoff are exceptionally brilliant. You will not find more experienced people in this field. Moreover their prices were far more competitive than the original equipment that was discarded. I cannot speak too highly of them and I would be happy to confirm my recommendation should you wish to speak to me personally. Do not hesitate to ask either Rej or Geoff for my phone number."- JAMES MOORE, ST IVES NSW


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- Research article
- Open Access
- Open Peer Review
Monocytes/macrophages support mammary tumor invasivity by co-secreting lineage-specific EGFR ligands and a STAT3 activator
© Vlaicu et al.; licensee BioMed Central Ltd. 2013
- Received: 29 December 2012
- Accepted: 8 April 2013
- Published: 18 April 2013
Tumor-associated macrophages (TAM) promote malignant progression, yet the repertoire of oncogenic factors secreted by TAM has not been clearly defined. We sought to analyze which EGFR- and STAT3-activating factors are secreted by monocytes/macrophages exposed to tumor cell-secreted factors.
Following exposure of primary human monocytes and macrophages to supernatants of a variety of tumor cell lines, we have analyzed transcript and secreted protein levels of EGFR family ligands and of STAT3 activators. To validate our findings, we have analyzed TAM infiltration levels, systemic and local protein levels as well as clinical data of primary breast cancer patients.
Primary human monocytes and macrophages respond to tumor cell-derived factors by secreting EGFR- and STAT3-activating ligands, thus inducing two important oncogenic pathways in carcinoma cells. Tumor cell-secreted factors trigger two stereotype secretory profiles in peripheral blood monocytes and differentiated macrophages: monocytes secrete epiregulin (EREG) and oncostatin-M (OSM), while macrophages secrete heparin-binding EGF-like growth factor (HB-EGF) and OSM. HB-EGF and OSM cooperatively induce tumor cell chemotaxis. HB-EGF and OSM are co-expressed by TAM in breast carcinoma patients, and plasma levels of both ligands correlate strongly. Elevated HB-EGF levels accompany TAM infiltration, tumor growth and dissemination in patients with invasive disease.
Our work identifies systemic markers for TAM involvement in cancer progression, with the potential to be developed into molecular targets in cancer therapy.
- Macrophage
- Monocyte
- Breast
- Carcinoma
- Patient
- Marker
- Progression
Molecular targeting of cancer cells has proven to be an extremely effective approach in tumor therapy. However, the inherent genomic instability of tumor cells promotes the establishment of therapy-refractory cancer cell clones during the course of treatment [1].
In addition, recent studies of the tumor microenvironment have emphasised that cancer cells effectively reprogram infiltrating immune cells, to the point where they support malignant progression [2]. Tumor-associated macrophages (TAM) are key participants in the crosstalk between tumor and immune cells. Thus, these genomically stable cells represent promising targets for anticancer therapy. TAM density correlates with poor prognosis in a considerable number of human cancers [3]. Their best studied contribution to malignancy is the involvement in tumor progression. In a mouse breast carcinoma model, Pollard and colleagues have shown that macrophage (MΦ) ablation inhibits metastasis [4]. MΦ exert important functions as trophic agents by secreting a plethora of growth factors and metalloproteases [5, 6]. With TAM being the most thoroughly studied components of the innate immune system, less is known about the impact of tumor-associated monocytes on tumor progression. Yet, populations of Tie2+ infiltrating monocytes promote angiogenesis in a mouse tumor model [7].
We studied the influence of tumor cells on ligand transcription and secretion patterns of monocytes and differentiated macrophages. Given the pivotal roles the oncogenic STAT3 and EGFR pathways play in tumor development [8, 9], we focused primarily on the repertoire of interleukin-6-like STAT3 activators and EGFR agonists secreted by tumor-primed monocytes and MΦ. Apart its founder protein, the interleukin-6 cytokine family includes interleukin-11 (IL-11), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin-M (OSM). The group of epidermal growth factor-like ligands contains seven EGFR agonists: amphiregulin (AREG), betacellulin (BTC), epidermal growth factor (EGF), epigen (EPGN), epiregulin (EREG), heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFα). Several lines of evidence point to a role of TAM-secreted EGFR ligands in malignant progression. McGee and colleagues provided clues for EGF production by TAM in breast carcinoma biopsies [10]. TAM number and EGFR expression levels correlate in human breast tumors [11], and TAM induce the EGFR-dependent migration of tumor cells in a murine breast carcinoma model [12]. However, the exact repertoire of TAM-secreted EGFR agonists is unknown, as are the related regulatory pathways.
Our work demonstrates that in response to tumor cell-derived factors, mononuclear cells in turn secrete oncogenic ligands. Subsequent to priming with tumor cell-secreted factors, human primary MΦ and peripheral blood monocytes (PBMC) both secrete OSM, but each cell type in combination with one specific EGFR agonist. These findings reveal characteristic secretory patterns of tumor-primed MΦ and PBMC in vitro, regardless of tumor etiology.
Ethics statement
This study was approved by the responsible ethics committee of the Ludwig-Maximilians-University, Munich, project nr. 189-11.
Cell lines
HL-60, MDA-MB-231, T-47D, MCF7, MDA-MB-468, MDA-MB-435S, SCC-9 and MCF 10A cell lines were obtained from the American Type Culture Collection (Manassas, VA). Primary HMEC were obtained from Clonetics (Basel, Switzerland) and cultured in MEGM® medium (Lonza, Walkersville, MD). HL-60, MDA-MB-231, MCF7, MDA-MB-468 and MDA-MB-435S cells were cultured in RPMI1640 containing 10% heat-inactivated fetal bovine serum (Invitrogen, Grand Island, NY). T-47D cells were cultured in RPMI1640 containing 10% heat-inactivated fetal bovine serum and 10 μg/ml bovine insulin (Sigma, St. Louis, MO). SCC-9 cells were cultured in DMEM/Ham's F-12 (1:1) containing 10% heat-inactivated fetal bovine serum and 0.4 μg/ml hydrocortisone (Sigma). MCF 10A cells were cultured in DMEM/Ham's F-12 (1:1) containing 5% heat-inactivated horse serum (Invitrogen), 0.5 μg/ml hydrocortisone, 20 ng/ml EGF (PeproTech, Hamburg, Germany), 10 μg/ml bovine insulin, 0.1 μg/ml cholera toxin (Sigma). All culture media contained 100 Units/ml Penicillin and 0.1 mg/ml Streptomycin (PAA, Pasching, Austria). Cells were cultured at 37°C in humidified air under 5% CO2 and were confirmed to be devoid of mycoplasma.
Monocyte isolation and macrophage differentiation
Peripheral blood was collected from healthy human donors after obtaining informed written consent. 15 ml of EDTA-treated blood were layered over a Ficoll-Paque™ PLUS column (GE Healthcare, Piscataway, NJ) and centrifuged at 400 g for 30 minutes, at 18°C. Leukocytes were washed twice with ice-cold PBS and transferred into RPMI containing 10% heat-inactivated fetal bovine serum and 5% active human serum. Following adherence to gelatine-coated culture plates (Sigma) that had been freshly precoated with human plasma, monocytes were washed 5 times with warm washing buffer (RPMI and PBS; 1:1), then detached using 5 mM EDTA in washing buffer. Cells were collected, centrifuged at 400 g for 15 minutes at 4°C then washed twice with ice-cold washing buffer. PBMC were plated at a density of 1.0 × 106 cells/ml in 6 well culture plates (Corning, Corning, NY) in monocyte culture medium (RPMI supplemented with 5% normal human male AB serum, Sigma). After 4 days of cultivation, cells were washed 3 times with RPMI and received fresh culture medium. Between day 4 and 10, medium was changed every third day. After 7 days of culture, macrophages had completed spontaneous differentiation.
Migration assays
Unless otherwise stated, cells were plated into transwell migration inserts (BD Biosciences, Bedford, MA) using RPMI + 0.1% BSA. The lower compartments contained either serum-free MΦ supernatants, culture media or RPMI + 0.1% BSA with or without OSM/HB-EGF. Where indicated, a 1 hr preincubation with neutralising antibodies, DMSO or AG1478 was performed prior to cell plating. At the end of the migration period, cells were fixed and stained with 20% methanol, 0.5% crystal violet and cotton swabs were used to remove the cells from the upper side of the membrane. An Axio Observer.A1 microscope (Carl Zeiss, Jena, Germany) was used to record 5 micrographs per well. Photoshop CS4 (Adobe, San Jose, CA) and a proprietary script were used for automated quantification of migration 5 × 104 SCC-9 cells were allowed to migrate for 6 hrs (chemotaxis) or 17 hrs (intrinsic motility). 1.5 × 105 MCF 10A cells were allowed to migrate for 17 hrs. 1.5 × 105 MCF7 cells were allowed to migrate for 48 hrs.
Statistical analysis
Two-tailed Mann–Whitney U-Tests were used for qPCR and ELISA experiments. For immunoblot, motility and chemotaxis experiments we used the two-tailed Student's T-Test. Differences were considered significant when p < 0.05. Data are presented as means ± SEM or SD.
Tumor cells and primary mononuclear cells interact via secreted factors
Tumor cell-derived factors trigger divergent patterns of transcriptional activity and ligand secretion in PBMC and MΦ
Together, these data indicate that that EREG, TGFA and OSM transcription is induced in PBMC upon priming with MDA-MB-231 supernatants. However, PBMC only secrete functionally active EREG and OSM proteins.
Priming of differentiated macrophages significantly increased HBEGF, AREG and OSM transcript levels (Figure 2D). EREG levels, though upregulated in primed MΦ, generally remain low in this cell type (Additional file 1: Figure S1C). Upon priming, MΦ supernatants significantly upregulated pEGFR levels in the reporter cell line, an effect which was completely blocked by an inhibitory antibody against HB-EGF. Though AREG transcription was highly upregulated, a neutralising antibody directed against AREG had no effect (Figure 2E). Supernatants of primed MΦ significantly elevated pSTAT3 levels in the reporter cell line, and an antibody blocking OSM function neutralised this effect (Figure 2E). Priming of differentiated MΦ for seven days provoked secretion of EGF family ligands and OSM to a similar extent (data not shown). Quantitation of secreted HB-EGF and OSM levels confirmed that secretion is significantly increased by priming (Figure 2F). In contrast, AREG was not secreted by primed MΦ (data not shown).
Taken together, these data indicate that, even though various EGFR ligands are transcriptionally induced, primed macrophages only secrete functionally active HB-EGF and OSM.
Tumor-primed PBMC and MΦ display specific secretory patterns
Tumor-primed PBMC and MΦ secrete one specific EGFR agonist, respectively, in combination with OSM, the relevant STAT3 activator. We next asked whether priming with an expanded panel of tumor cell supernatants provokes similar response patterns in PBMC and MΦ. The panel contained MDA-MB-231 (231), T-47D (T47), MCF7 (7), MDA-MB-468 (468) invasive mammary and SCC-9 (SCC) squamous carcinoma cell lines. MCF 10A (10A) are derived from a benign breast lesion and primary HMEC (HM) represent healthy breast epithelium.
Tumor-secreted factors induce specific secretory patterns in PBMC and MΦ
Priming supernatant
MΦ primed by 231, T47, 7 and SCC co-secreted considerable amounts of HB-EGF and OSM (Table 1, Additional file 1: Figure S6B), which were shown to be the only EGFR and STAT3 activators released by primed MΦ (Additional file 1: Figure S6C/D).
We observed clearly distinct priming capacities of tumor cell lines on primary mononuclear cells: primary breast epithelial cells (HM) derived from healthy donors neither convey a secretory response in PBMC nor in MΦ (Table 1, Additional file 1: Figure S5/S6). Selective PBMC priming was achieved by 10A and 468 cells, while 7 and SCC cells exclusively primed MΦ. 231 and T47 breast carcinoma cells primed PBMC as well as MΦ (Table 1). Thus, a number of tumor cell lines triggers PBMC and MΦ to co-secrete an EGFR agonist and a STAT3 activator. The secretory patterns of tumor-primed mononuclear cells are lineage-specific: PBMC co-secrete EREG and OSM, while MΦ co-secrete HB-EGF and OSM.
HB-EGF and OSM are promigratory in epithelial cells
Though originally reported as an antiproliferative factor [20], OSM failed to inhibit proliferation of several breast cancer cell lines (Additional file 1: Figure S7A). However, OSM induces the undirected motility of MCF7 cells [21]. We incubated MCF7 cells for five days at increasing doses of recombinant OSM. The Boyden chamber assay confirmed a dose-dependent increase in undirected MCF7 cell motility (Figure 3B). Similarly, a 2.6-fold increase in undirected motility was observed in SCC-9 cells (Figure 3C).
10A, benign breast epithelial cells, are barely migratory under most assay conditions. OSM did not induce motility of 10A cells (data not shown). However, OSM-treated 10A cells migrated two to three times faster along an HB-EGF gradient (Figure 3D). For this cell line, HB-EGF is a potent mitogen (Additional file 1: Figure S7B).
Taken together, prolonged treatment of MCF7 and SCC cells with recombinant OSM induces undirected motility in these tumor cells. Priming of MΦ by tumor cells results in HB-EGF secretion at levels sufficient to drive cell migration, and HB-EGF is the relevant chemotactic factor for SCC cells secreted by primed MΦ. OSM and HB-EGF cooperate in promoting chemotaxis of MCF 10A epithelial cells. All three cell lines express receptors for OSM (Additional file 1: Figure S2) and EGFR (Additional file 1: Figure S6A), [22, 23].
TAM express HB-EGF/OSM in invasive breast carcinoma and HB-EGF plasma levels correlate with primary tumor growth and lymph node involvement
Given that HB-EGF levels were elevated in a larger proportion of patients' plasma samples, we reasoned that HB-EGF plasma levels might correlate with growth and/or progression of mammary carcinomas. Mean plasma concentrations of HB-EGF reflect primary tumor size: for small tumors (pT1; 23 patients) we detected 29.6 pg/ml, medium sized tumors (pT2; 13 patients) displayed 62.1 pg/ml and large tumors (pT3; 9 patients) 131.8 pg/ml. In conclusion, HB-EGF plasma levels correlated with primary tumor size (Figure 4B).
In addition, elevated HB-EGF plasma levels also correlate with lymph node dissemination of mammary breast carcinomas (Figure 4C): healthy donors (Ctrl; n = 26) and lymph node negative invasive mammary carcinoma patients (pN0; n = 26) displayed mean HB-EGF plasma concentrations of 21.2 pg/ml and 24.6 pg/ml, respectively, whereas significantly elevated HB-EGF levels were detected in patients with disseminated tumors (97.5 pg/ml; pN > 0; n = 28).
We defined the mean plasma HB-EGF concentration of healthy donors (21.2 pg/ml; Figure 4A) as a threshold that grouped invasive breast carcinoma patients into an HB-EGF negative or HB-EGF positive cohort. In this scoring, 50% (27 of 54) of the patients were determined HB-EGF positive, and tumor cell positive lymph nodes were detected in 52% (28 of 54) of the patients. However, 70% (19 of 27) of HB-EGF positive patients were diagnosed with disseminated tumors, whereas only 33% (9 of 27) of the HB-EGF negative cohort were lymph node positive (Figure 4D). In conclusion, mammary carcinoma patients with disseminated tumors can be identified by elevated HB-EGF plasma levels.
To test a potential participation of monocyte-secreted EREG in the development of mammary tumors, we quantified EREG plasma protein levels in 59 donors with DCIS or invasive mammary carcinomas as well as in 10 healthy donors. In the control donors and in the majority of breast cancer patients, EREG plasma levels remained low (Additional file 1: Figure S9). We only detected elevated EREG levels in 5 of 59 cancer patients, rendering a significant contribution of monocyte-derived EREG to the progression of breast cancer implausible. A supplementary list containing ELISA and clinical patient data is available online (Additional file 2).
Confirming our in vitro interaction model, the presented immunohistochemical data identify TAM as sources of production of HB-EGF and OSM in primary tumors. Elevated HB-EGF and OSM levels in patients' plasma indicate secretion of both ligands by TAM in mammary carcinomas in vivo.
Given the strong correlation between TAM density, HB-EGF plasma levels and tumor size, increased HB-EGF plasma levels identify a substantial part of node positive patients, connecting TAM-secreted HB-EGF with tumor dissemination.
Tumor HBEGFexpression is predominantly localised in the stromal compartment
To further substantiate the clinical data, we analysed tumor microarray datasets available at Oncomine™. The breast carcinoma microarray dataset by Ambs and colleagues distinguished between genes expressed by tumor cells versus stromal cells [24]. Our analysis of this dataset revealed that both HBEGF and the monocytic marker CD64 are predominantly expressed in the stromal compartment (Additional file 1: Figure S10A), suggesting that tumor-associated mononuclear cells express this EGFR agonist.
In our experiments, priming of differentiated MΦ was not restricted to mammary carcinoma cell lines. MΦ-derived factors are also functional in other carcinomas. Analysis of the bladder carcinoma microarray dataset published by Radvanyi and colleagues [25] showed HBEGF to be overrepresented in infiltrating carcinoma samples (Additional file 1: Figure S10B). These data corroborate our in vitro findings that HB-EGF is involved in the progression of a variety of carcinomas.
Recent scientific advances have established that monocytes and macrophages are not only critically involved in inflammatory processes such as pathogen defence and wound healing, but also play an active role in cancer development. Their functions are modulated by tumor cells, resulting in tolerant, trophic phenotypes indispensable for tumor progression [6]. Among the factors secreted by tumor cells the chemokine CCL2 has been identified as an important priming factor of TAM in vivo[26]. Based on a model that tumor cells and mononuclear cells communicate via secreted factors, we have used cell supernatants to study the reciprocal influence of both cell types. Our main focus was on the paracrine release of both EGFR and STAT3 activators by monocytes/macrophages to tumor cells [6]. The presented data indicate that the differentiation process of monocytes to macrophages is of no importance for the activation of these two signaling pathways, even though the precise nature of the secreted ligands changes with differentiation.
Constitutive activation of STAT3 is common in melanoma, breast, head and neck, lung, pancreatic and prostate cancer [27]. Tumor-primed primary PBMC and MΦ secrete oncostatin-M, and only OSM activates STAT3 in our reporter system. Both OSM receptors are exclusively found in epithelial and carcinoma cells. This underscores the unique paracrine role of mononuclear cell-derived OSM acting on tumor cells. This is the first report that shows tumor cell-derived activities to induce OSM secretion by primary human PBMC and MΦ, supporting an interaction model defined by mutually secreted factors. All of the tested tumor cell lines effectively primed human PBMC and/or differentiated MΦ. Priming induced rather complex transcriptional induction profiles of EGFR ligands in mononuclear cells. At protein level, however, priming resulted in co-secretion of EREG and OSM by PBMC, while tumor-primed MΦ co-secreted HB-EGF and OSM in vitro. Transcript analysis alone, however, would not reliably predict the functionally relevant EGFR agonist released by tumor-primed mononuclear cells [28]. In summary, two secretory patterns emerge in PBMC and MΦ in response to tumor cell-secreted factors: a lineage-specific EGFR ligand in combination with OSM.
Functionally, recombinant OSM and HB-EGF strongly cooperate in inducing chemotaxis of benign breast cells in vitro. OSM enhances the intrinsic motility of carcinoma cells, while macrophage-produced HB-EGF is the key chemotactic factor for squamous cell carcinoma cells in our assays. Our in vitro data suggest that TAM-derived OSM and HB-EGF influence migratory processes of cancer cells. In breast cancer patients, HB-EGF and OSM are co-expressed by TAM and plasma protein levels of both ligands correlate strongly. Elevated HB-EGF plasma protein levels are strongly associated with primary tumor growth and lymph node dissemination in invasive breast cancer patients. In fact, the majority of lymph node positive patients display elevated HB-EGF plasma levels. Increased density of infiltrating TAM in patients with elevated HB-EGF plasma levels further supports the hypothesis that TAM-secreted HB-EGF promotes breast carcinoma growth and metastasis in vivo. HBEGF transcripts primarily detected in the stroma of mammary carcinomas correlate with the myeloid marker CD64, further supporting the assumption that TAM account for the expression of HBEGF in the tumor microenvironment. Our analysis of the Stransky bladder carcinoma microarray data [25] corroborated these findings inasmuch as HBEGF transcript levels increase in infiltrating tumors with respect to superficially growing lesions. In bladder carcinomas, HBEGF transcript levels inversely correlate with patients' survival times [19]. As Massagué and co-workers have shown in a mouse xenograft model, HBEGF sustains the specific dissemination of human mammary tumor cells to the brain, whereas dissemination to the lung is accompanied by EREG expression [29, 30]. Elevated EREG plasma protein levels, however, were detected in a minor fraction of our breast cancer patient data set, suggesting that EREG is not a primary contributor to breast cancer progression mediated by monocytes in humans. Immunohistochemical studies of HB-EGF expression in breast carcinoma tumor cells have found no [31] or an inverse correlation [32] to tumor progression parameters, whereas our study indicates a positive contribution of TAM-derived HB-EGF production in the primary tumor to invasive mammary carcinoma progression. TAM expression of HB-EGF has been reported for cholangiocarcinoma metastases. Additionally, this report linked the priming of mononuclear cells to HB-EGF expression in vitro [33].
Inflammatory processes have been studied in wound healing, and macrophages play a key role in skin repair [34]. In this process, only infiltrating polymorphonuclear neutrophils have yet been described to secrete OSM [35], and HB-EGF is detected in wound exudates [36].
Our work focuses on paracrine factors secreted by mononuclear cells upon priming by tumor cells. This priming process induces secretory patterns that consistently feed back to activate oncogenic EGFR- and STAT3 pathways in tumor cells. We identify HB-EGF and OSM as the key EGFR and STAT3 activators secreted by tumor-primed MΦ, and EREG and OSM as the key activating factors secreted by tumor-primed PBMC. HB-EGF and OSM profoundly influence tumor cell behaviour and cooperatively promote cell motility. Our in vitro results indicate that these proteins effectively mediate macrophage-assisted cancer progression. The identified stereotype secretion patterns are elementary to design strategies to interfere with pro-tumorigenic mononuclear functions by inhibiting HB-EGF, EREG and OSM. In particular, HB-EGF function is apparently connected to tumor growth and dissemination. But first, a clear clinical characterisation of the subset of tumors infiltrated by pro-tumorigenic mononuclear cells is essential. In particular, HB-EGF serves as potential blood-bound marker allowing the minimally invasive identification of tumors supported by TAM. Our work describes pro-tumorigenic marker proteins that identify tumor-supportive mononuclear cells and establishes a basis for therapeutic intervention aimed at neutralising these STAT3 and EGFR activators at the molecular level.
Soluble tumor-cell-derived factors trigger mononuclear cells to co-secrete lineage-specific EGFR agonists together with a common STAT3 activator. Tumor-primed MΦ release HB-EGF and OSM, while tumor-primed PBMC co-secrete EREG and OSM. TAM co-express HB-EGF and OSM in primary mammary carcinoma samples. In these patients, HB-EGF plasma protein levels strongly correlate with TAM infiltration levels, primary tumor size and lymph node dissemination, indicating that TAM-derived HB-EGF supports carcinoma progression. Thus, HB-EGF plasma protein levels are a potential marker indicating a pro-tumor reaction of TAM in mammary carcinoma.
The authors thank all blood donors at the Department of Molecular Biology, Max Planck Institute of Biochemistry, as well as Monika Sommer and Joerg Reichert for collecting the blood samples. We thank Tatjana Knyazeva for preparing cDNA samples. We thank Esther Zwick-Wallasch at U3 Pharma, Martinsried, for kindly providing an anti-HB-EGF antibody. Furthermore, we thank Angela Gunesch and Kerstin Badlehner as well as Johanna Schuster, Red Cross Women's Hospital, Munich, for retrieval of patient data, and Sebastian Kaiser, LMU Munich, for help with statistical analysis.
Authors' Affiliations
- Politi K, Fan PD, Shen R, Zakowski M, Varmus H: Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinoma. Dis Model Mech. 2010, 3 (1–2): 111-119.View ArticlePubMedGoogle Scholar
- Johansson M, Denardo DG, Coussens LM: Polarized immune responses differentially regulate cancer development. Immunol Rev. 2008, 222: 145-154. 10.1111/j.1600-065X.2008.00600.x.View ArticlePubMedPubMed CentralGoogle Scholar
- Bingle L, Brown NJ, Lewis CE: The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002, 196 (3): 254-265. 10.1002/path.1027.View ArticlePubMedGoogle Scholar
- Lin EY, Nguyen AV, Russell RG, Pollard JW: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001, 193 (6): 727-740. 10.1084/jem.193.6.727.View ArticlePubMedPubMed CentralGoogle Scholar
- Martin P, Leibovich SJ: Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 2005, 15 (11): 599-607. 10.1016/j.tcb.2005.09.002.View ArticlePubMedGoogle Scholar
- Pollard JW: Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004, 4 (1): 71-78. 10.1038/nrc1256.View ArticlePubMedGoogle Scholar
- De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L: Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell. 2005, 8 (3): 211-226. 10.1016/j.ccr.2005.08.002.View ArticlePubMedGoogle Scholar
- Yu H, Kortylewski M, Pardoll D: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 2007, 7 (1): 41-51. 10.1038/nri1995.View ArticlePubMedGoogle Scholar
- Hynes NE, Lane HA: ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005, 5 (5): 341-354. 10.1038/nrc1609.View ArticlePubMedGoogle Scholar
- O'Sullivan C, Lewis CE, Harris AL, McGee JO: Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet. 1993, 342 (8864): 148-149. 10.1016/0140-6736(93)91348-P.View ArticlePubMedGoogle Scholar
- Leek RD, Hunt NC, Landers RJ, Lewis CE, Royds JA, Harris AL: Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J Pathol. 2000, 190 (4): 430-436. 10.1002/(SICI)1096-9896(200003)190:4<430::AID-PATH538>3.0.CO;2-6.View ArticlePubMedGoogle Scholar
- Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J: A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004, 64 (19): 7022-7029. 10.1158/0008-5472.CAN-04-1449.View ArticlePubMedGoogle Scholar
- Mantovani A, Bottazzi B, Sozzani S, Peri G, Allavena P, Dong QG, Vecchi A, Colotta F: Cytokine regulation of monocyte recruitment. Arch Immunol Ther Exp (Warsz). 1995, 43 (2): 149-152.Google Scholar
- Gschwind A, Prenzel N, Ullrich A: Lysophosphatidic acid-induced squamous cell carcinoma cell proliferation and motility involves epidermal growth factor receptor signal transactivation. Cancer Res. 2002, 62 (21): 6329-6336.PubMedGoogle Scholar
- Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M: A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991, 251 (4996): 936-939. 10.1126/science.1840698.View ArticlePubMedGoogle Scholar
- Nishi E, Klagsbrun M: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a mediator of multiple physiological and pathological pathways. Growth Factors. 2004, 22 (4): 253-260. 10.1080/08977190400008448.View ArticlePubMedGoogle Scholar
- Miyamoto S, Hirata M, Yamazaki A, Kageyama T, Hasuwa H, Mizushima H, Tanaka Y, Yagi H, Sonoda K, Kai M: Heparin-binding EGF-like growth factor is a promising target for ovarian cancer therapy. Cancer Res. 2004, 64 (16): 5720-5727. 10.1158/0008-5472.CAN-04-0811.View ArticlePubMedGoogle Scholar
- Tanaka Y, Miyamoto S, Suzuki SO, Oki E, Yagi H, Sonoda K, Yamazaki A, Mizushima H, Maehara Y, Mekada E: Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res. 2005, 11 (13): 4783-4792. 10.1158/1078-0432.CCR-04-1426.View ArticlePubMedGoogle Scholar
- Thogersen VB, Sorensen BS, Poulsen SS, Orntoft TF, Wolf H, Nexo E: A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients. Cancer Res. 2001, 61 (16): 6227-6233.PubMedGoogle Scholar
- Zarling JM, Shoyab M, Marquardt H, Hanson MB, Lioubin MN, Todaro GJ: Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci USA. 1986, 83 (24): 9739-9743. 10.1073/pnas.83.24.9739.View ArticlePubMedPubMed CentralGoogle Scholar
- Zhang F, Li C, Halfter H, Liu J: Delineating an oncostatin M-activated STAT3 signaling pathway that coordinates the expression of genes involved in cell cycle regulation and extracellular matrix deposition of MCF-7 cells. Oncogene. 2003, 22 (6): 894-905. 10.1038/sj.onc.1206158.View ArticlePubMedGoogle Scholar
- Boylan M, van den Berg HW, Lynch M: The anti-proliferative effect of suramin towards tamoxifen-sensitive and resistant human breast cancer cell lines in relation to expression of receptors for epidermal growth factor and insulin-like growth factor-I: growth stimulation in the presence of tamoxifen. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO. 1998, 9 (2): 205-211. 10.1023/A:1008241804078.View ArticleGoogle Scholar
- Martinez-Lacaci I, Kannan S, De Santis M, Bianco C, Kim N, Wallace-Jones B, Ebert AD, Wechselberger C, Salomon DS: RAS transformation causes sustained activation of epidermal growth factor receptor and elevation of mitogen-activated protein kinase in human mammary epithelial cells. International journal of cancer Journal international du cancer. 2000, 88 (1): 44-52. 10.1002/1097-0215(20001001)88:1<44::AID-IJC7>3.0.CO;2-8.View ArticlePubMedGoogle Scholar
- Boersma BJ, Reimers M, Yi M, Ludwig JA, Luke BT, Stephens RM, Yfantis HG, Lee DH, Weinstein JN, Ambs S: A stromal gene signature associated with inflammatory breast cancer. Int J Cancer. 2008, 122 (6): 1324-1332.View ArticlePubMedGoogle Scholar
- Stransky N, Vallot C, Reyal F, Bernard-Pierrot I, de Medina SG, Segraves R, de Rycke Y, Elvin P, Cassidy A, Spraggon C: Regional copy number-independent deregulation of transcription in cancer. Nat Genet. 2006, 38 (12): 1386-1396. 10.1038/ng1923.View ArticlePubMedGoogle Scholar
- Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW: CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011, 475 (7355): 222-225. 10.1038/nature10138.View ArticlePubMedPubMed CentralGoogle Scholar
- Yu H, Jove R: The STATs of cancer–new molecular targets come of age. Nat Rev Cancer. 2004, 4 (2): 97-105. 10.1038/nrc1275.View ArticlePubMedGoogle Scholar
- Subimerb C, Pinlaor S, Lulitanond V, Khuntikeo N, Okada S, McGrath MS, Wongkham S: Circulating CD14(+) CD16(+) monocyte levels predict tissue invasive character of cholangiocarcinoma. Clin Exp Immunol. 2010, 161 (3): 471-479. 10.1111/j.1365-2249.2010.04200.x.View ArticlePubMedPubMed CentralGoogle Scholar
- Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J: Genes that mediate breast cancer metastasis to lung. Nature. 2005, 436 (7050): 518-524. 10.1038/nature03799.View ArticlePubMedPubMed CentralGoogle Scholar
- Bos PD, Zhang XH, Nadal C, Shu W, Gomis RR, Nguyen DX, Minn AJ, van de Vijver MJ, Gerald WL, Foekens JA: Genes that mediate breast cancer metastasis to the brain. Nature. 2009, 459 (7249): 1005-1009. 10.1038/nature08021.View ArticlePubMedPubMed CentralGoogle Scholar
- Suo Z, Risberg B, Karlsson MG, Villman K, Skovlund E, Nesland JM: The expression of EGFR family ligands in breast carcinomas. Int J Surg Pathol. 2002, 10 (2): 91-99. 10.1177/106689690201000202.View ArticlePubMedGoogle Scholar
- Ito Y, Takeda T, Higashiyama S, Noguchi S, Matsuura N: Expression of heparin-binding epidermal growth factor-like growth factor in breast carcinoma. Breast Cancer Res Treat. 2001, 67 (1): 81-85. 10.1023/A:1010667108371.View ArticlePubMedGoogle Scholar
- Rigo A, Gottardi M, Zamo A, Mauri P, Bonifacio M, Krampera M, Damiani E, Pizzolo G, Vinante F: Macrophages may promote cancer growth via a GM-CSF/HB-EGF paracrine loop that is enhanced by CXCL12. Mol Cancer. 2010, 9 (1): 273-10.1186/1476-4598-9-273.View ArticlePubMedPubMed CentralGoogle Scholar
- Lucas T, Waisman A, Ranjan R, Roes J, Krieg T, Muller W, Roers A, Eming SA: Differential roles of macrophages in diverse phases of skin repair. J Immunol. 2010, 184 (7): 3964-3977. 10.4049/jimmunol.0903356.View ArticlePubMedGoogle Scholar
- Goren I, Kampfer H, Muller E, Schiefelbein D, Pfeilschifter J, Frank S: Oncostatin M expression is functionally connected to neutrophils in the early inflammatory phase of skin repair: implications for normal and diabetes-impaired wounds. J Invest Dermatol. 2006, 126 (3): 628-637. 10.1038/sj.jid.5700136.View ArticlePubMedGoogle Scholar
- Marikovsky M, Breuing K, Liu PY, Eriksson E, Higashiyama S, Farber P, Abraham J, Klagsbrun M: Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci USA. 1993, 90 (9): 3889-3893. 10.1073/pnas.90.9.3889.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/197/prepub
Pre-publication history
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
Plant Manager - Renewable Energy
|Job Title:
|Plant Manager - Renewable Energy
|Contract Type:
|Cardigan, Ceredigion
|£40000 - £55000 per annum + benefits
|Contact Name:
|Cherie Moore
|Contact Email:
|Job Published:
|June 22, 2018 14:01
Job Description
Plant Manager - Renewable Energy
Up to £55,000
Aberteifi, Wales
We are currently seeking to recruit an experienced Renewable Energy / Waste / Process Plant Manager, to oversee and manage the daily operations of an advanced process plant based near the West coast of Wales. Our client is an industry leader within its field, with the opportunity for an experienced Plant Manager to join their team.
As Plant Manager, you will be responsible for:
- Managing all operational activities on site
- Leading the technical maintenance of the site to optimise process equipment performance, uptime, biogas production and energy generation.
- Managing variety of feedstock materials to maintain and optimise feedstock mix to drive maximum biogas yield
- Dealing with all personnel issues in line with company policies and procedures.
- Managing the commercial element of the business, ensuring all activities are closely analysed, recorded and reported, clearly justifying any decision made.
- Analysing and reporting on feedstock characteristics and digester health. Determining optimum feeding regime
- P&L responsibility
- Ensuring Health & Safety is adhered to at all times
- Ensuring efficient operations of the plant to meet KPIs
- Other duties as required
To be considered for this position, you must have proven experience working in the waste processing / generation industry in a Management focused position. You will ideally hold a Chemical/Process Engineering degree or equivalent experience, WAMITAB training is desirable and you should have a good knowledge of feedstocks and be able to analyse lab results.
The package on offer for this position includes an attractive basic salary up to £55,000 (dependant on experience), plus pension, holidays. You must be eligible to work in the UK.
If you are interested in applying for this role, please email a copy of your latest CV to email@example.com or call Cherie Moore on 02392 288 217.
Astute Technical Recruitment Limited are acting as an employment agency in relation to this vacancy. We do not discriminate on the grounds of age, race, gender, disability, creed or sexual orientation and comply with all relevant UK legislation. We encourage applications from individuals from all backgrounds but candidates must be able to demonstrate their ability to work in the UK and Europe. We endeavour to get back to everyone, however, if you have not heard anything after 7 days, please consider your application unsuccessful.
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I hope everyone is enjoying Wok Wednesdays so far. We've only just begun but I am getting great feedback from many of you wokkers and I'm so happy that we're learning the ways of the wok together.
I'm also happy to announce another Wok giveaway! The 14-inch flat-bottomed carbon steel wok is the wok of choice for Grace Young, and the most practical wok for home kitchens. Thanks to Tane Chen of The Wok Shop in San Francisco you now have a chance to win your very own wok. Perhaps you have been stir-frying with a large skillet or you have a scratched-up nonstick wok that you need to replace. Perhaps you just want two woks! Either way, all you have to do to enter is leave a comment below answering the following question:
As a stir-fry newbie was it difficult or intimidating getting used to high heat cooking?
Leave your answer by 11:59pm EST, Friday June 8th.
– Matt


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Urethane Dunnage Manufactured to provide maximum protection to delicate parts during transport
Provides shock and vibration protection for fragile parts
Secure parts and packages during transport!
Formulated urethanes made to the exact density (hardness) you require
We Serve the Best Companies Around the World
Product Description
TPC Urethane Inc. custom molded urethane dunnage is provides superior part protection during all stages of assembly and shipping, offers the ideal solution to assembly line damage problems and is non-marking. Dunnage material packaging is necessary in transporting in industries such as, manufacturing, electronics, automotive, food, and medical.TPC Urethane Inc.has been producing a large array of dunnage parts for over thirty years.
Technical Specifications
- Custom urethane dunnage systems
- non-marking
- Performance that you can rely on
- Superior construction processes
- Serving a wide range of shipping industries
- Complete protection for your cargo
Family Owned & Operated Since 1972
We have been casting high quality urethane products for over 40 years. Our goal is to provide our customers with the highest grade urethane products with on-time deliveries at a highly competitive price. From a single part to mass production no run is to big or too small for our state of the art equipment.
Contact Us


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Just signed a short story over to Goodman Games! It'll be featured in Tales From the Magician's Skull #2, which should be available this summer.
To a mage, water carries memories. Wine conveys the fears of those who made it. Rain whispers the darkest secrets of a city. Gatja may only use her gifts in service to the Order; or her magic will rip her mind apart.To a mage, stone carries power. Bones in the earth teach legacy. Lines in the sand dictate who lives and who dies; but Riad can no longer tell friend from enemy. Riad's family begs the Order for aid, and they send Gatja to assess and solve the problem.If only his family hadn't murdered hers.
This story was inspired by, and written while listening to, Í Tokuni by Faroese singer, Eivør.
It's my understanding that embedded links are copyright infringement, so here's a link to the video on YouTube. Check it out, and enjoy!


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The secular growth story for the exchange traded products continued last year as 2013 inflows checked in at a record $247.3 billion. That marks the second consecutive year inflows topped $200 billion.
Flows to U.S. ETFs and ETNs dominated at a combined $190.5 billion, according to BlackRock (BLK), the world's largest asset manager.
"ETFs continue to attract a broad base of global investors, driven by regional regulatory developments, deepening ETF liquidity, and increasing awareness among both retail and institutional clients of the benefits of ETFs. These efficient tools are being used by for all types of investors — from capital market participants looking for liquidity, to pension clients seeking specialized exposures, to a growing segment of the market using ETFs as buy and hold investment vehicles," said BlackRock Global Head of ETP Research Dodd Kittsley in a statement.
Digging deeper into the numbers, winning and losing asset classes become more apparent. For example, gold ETFs were stung by massive outflows in 2013. [2014 May Not be Much Better for Gold ETFs]
"Gold ETP outflows of ($40.1bn) in 2013 offset all inflows from the past three years combined as the price of Gold fell from its peak and investors turned to Equities for more attractive returns," according to BlackRock.
On the other hand, smart-beta, or non-cap weighted ETFs, continued to gain stature…and assets. Smart beta ETFs "contributed a record $65.1bn of inflows in 2013 led by dividend-weighted funds, and nearly doubled the $34.2bn from last year," said BlackRock. [Smart Beta ETFs Shine in 2013]
Despite their vulnerability to rising interest rates and claims that investors were looking for higher-beta fare, low volatility ETFs raked in $13.2 billion last year. U.S.-focused "low vol" ETFs lagged last year, but comparable funds offering exposure to emerging markets were significantly less bad than traditional ETFs focused on developing world equities. [Some Low Vol ETFs Worked in 2013]
Dividend ETFs pulled in $29 billion. Bond ETFs saw 2013 inflows of $27.5 billion due primarily to the $35.9 billion investors poured into short-duration funds.
"US ETP assets have grown at a 27% CAGR over the past 10 years. This compares to 7% for mutual funds. In 2013, US ETPs not only kept up with their historical pace by growing 26% but they also achieved the highest asset growth of all ETP regions for the year. Assets increased by $351.7bn, with flows of $190.5bn boosted by record market move for the industry of $161.2bn," according to BlackRock.
Top 10 ETFs 2013 Inflows
Table Courtesy: BlackRock
The opinions and forecasts expressed herein are solely those of Tom Lydon, and may not actually come to pass. Information on this site should not be used or construed as an offer to sell, a solicitation of an offer to buy, or a recommendation for any product.


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This is the outfit I wore for the Swarovsky event I had the pleasure of going to the other night. Champagne, mini tarts, and some of the most beautiful pieces from the current collection were the decorating elements inside the sparkling boutique of the brand right on Madison avenue.A few drinks later, I got the pleasure to get to know […]CONTINUE READING →
One of my favorite places in New York is the Dumbo park in Brooklyn. I think I will never get tired of the view of the city from there, especially at night. From the water, New York looks like a post card and I could stay there, sitting still on those steps for hours just watching the downtown skyscrapers […]CONTINUE READING →
One of the must haves of this spring/summer 2013 is undoubtely skorts. The perfect fusion between a pair of shorts and a skirt. The one I am wearing today is a kind courtesy of Mango, and they are the perfect item to wear and reinvent in a thousand and more different ways. I gave this ensenble a more sparkling […]CONTINUE READING →
Lately red has become an obsession for me. It feels so easy to pull something red out of my closet and find something else to go along with it. Today's red pieces are this beautiful Kay Unger skirt I bought a couple of weeks ago during one of my shopping seesions along with my Celine nano bag. Ultimamente la mia […]CONTINUE READING →
Today's pictures are bit different from the usual: a long BCBG dress with a siren shape, one of my favorite earrings and New York in the background. Have a good everybody! Le foto di oggi sono un po' piu' particolari del solito: un vestito lungo firmato BCBG e un paio tra i miei orecchini preferiti. New York sullo sfondo fa […]CONTINUE READING →


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Welcome to Haunted Littleton!
We host walking tours/ghost hunts through the heart of the Historic district in Littleton, North Carolina, located on US 158 between I-85 and I-95 is a town with a rich history going back to the revolutionary. One of the main coach roads running east and west through North Carolina ran right through town, and later a branch of the NC railroad ran through connecting Halifax and Raleigh.
The tour includes a house built in 1895, Person's Ordinary built in 1739 (the oldest historical landmark of Halifax county), and Lakeland theater based in what used to be the Littleton School which had all grades.
We will tell history of the area, ghost stories, and personal experiences as well as a brief lesson in using standard ghost hunting equipment.
For details on the tour, click here.
Please RSVP for a tour date here, as spots are limited.


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SAAPA's May 2013 2nd Saturday Program!
Photos from Family Fun Day for the Aerospace Academy, April 27, 2013:
General Aviation is under Government assault. Check out AOPA's News video:
SAAPA St. Patrick's Day Social!
The above St. Patrick's Day SAAPA Social highlights Video is viewable on Macs, but may NOT be viewable by some PCs, iPads or some smart phones. In that case, you will see a blank space immediately above this text.
St. Augustine Airport Pilots' Association is an Aviation Club.
SAAPA's Mission and Vision:
Mission: To Promote, Preserve and Protect the interests of the General Aviation Community at St. Augustine Airport.
Vision: To create and foster an environment that supports the enthusiasm of pilots and aviation enthusiasts, and to encourage the camaraderie of aviation and the support of the local community.
St. Augustine Airport Pilots' Association (known as "SAAPA") is an Aviation club comprised of over 200 members. Our members include non-pilots, pilots, and folks who understand that airplanes and aircraft are cool. If you have an interest in aircraft or Aviation, contact us about visiting one of our 1st Friday Socials!


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Teeth whitening treatments have become extremely popular in recent years and are now amongst the most asked for cosmetic dental treatments. Teeth whitening treatments can transform the appearance of the teeth in a matter of hours and give you a glossy, healthy looking smile.
Over the course of time, the natural whiteness of the teeth can fade and our day to day lifestyle, habits and diet can have an impact on the colour of the teeth. Many of us drink tea, red wine and coffee on a daily basis and this can gradually stain the teeth; smoking can also have a significant impact on the colour of the teeth. Whitening treatments can help to restore the natural whiteness of the teeth, boosting your confidence and giving you a smile to be proud of.
At Harley Street Dental Studio, we recognise the importance of a great looking smile and we are delighted to be able to offer our clients a comprehensive range of whitening treatments. Our treatments include:
Most people have heard about whitening treatments but choosing a treatment may be extremely confusing as there are so many different products, treatments and procedures on the market, all claiming to produce incredible results. If you don't know much about whitening treatments the list above may be a little daunting and confusing and you may be struggling to work out which treatment will suit you best. Our friendly team will be more than happy to discuss the different treatments with you and explain which treatment would be best for you. We have carefully selected the best range of treatments and are proud to offer these whitening methods to our patients.
If you want to know more about whitening treatment, contact our West End London office today to arrange a consultation. To help you find out which whitening treatment would be best for you, each respective treatment is explored in detail below:
Enlighten is our most highly recommended whitening treatment. The Enlighten whitening system was launched in 2001 and has subsequently become one of the most popular cosmetic dental treatments on the market. Enlighten is highly recommended by dentists because it guarantees incredible results, lightens teeth by up to 10 shades and lasts for several years.
The Enlighten whitening system includes a range of professional treatments and at-home products. For optimum results, we recommend a combination of in-house and at-home treatments.
If you are keen to find out about special offers on whitening treatments or you want to know more about our treatments, please get in touch with our West End office to arrange a consultation. The smile you've always dreamed of could be just around the corner.
If you would like to explore your teeth whitening options, contact our cosmetic dentist serving central London to schedule a consultation. Enlighten teeth whitening treatments are popular throughout the UK for brightening smiles.
In line with the new EU regulations 01/11/12 all our whitening products contain no more than 6% hydrogen peroxide or equivalent
*Enlighten Teeth Whitening Finance
6 months - £116.16 per month – 0% APR
10 months - £70.00 per month – 0% APR
12 months - £58.33 per month – 0% APR
Based off £700 treatment cost.


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Williams, the magazine ad states about Lanolin - rich Shaving Cream. This ad highly points that only very little or a drop of cream is more than enough for a good shave for men. It emphasize as ….
Why? Because Williams Shaving Cream is Lanolin- rich. That's why it's the only cream for you.
You get the smoothest, most comfortable shave from a lather that says rich and creamy your whole shave through.
And Williams saves you money. Thanks to the richness of Lanolin, you need less cream for every shave.
Choose from Williams Lanolin- rich or Williams Menthol.
For the most comfortable shave of your life!
Made by the DWilliams Aqua Velva people- so you know it is good!


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You used it, but you don't know …
It's so interesting to know that you usually use the version control in your work. Perhaps there are some files named with numbers like these in your computer:
- report-1.doc
- report-2.doc
- my_current_stuff_20110912.psd
- my_current_stuff_20111011.psd
- …
Why these file exist and have such names? You add a number or a date string to the end of the file name because you want to have a backup of your current work. If you go wrong in the future and want to have the latest good version, you can get it easily (may be not quickly). As you can see, version control plays an important roll in your work though you are not aware of it.
A version control system, huh, why do we need it?
A good version control system (VCS) will allow you to do the following stuff easily:
- Backup and restore: files are saved when you need. You can jump to a previous version any time. You can throw many recent change and roll back to the last good version in the database. You can all so get the code from last year and what have changed when getting a bug.
- Synchronization: all people can have a up-to-date version easily.
- Track changes and ownership: the VCS can store the information about changes in you files and who the person who made it, which make you easily to see how a file is evolving over time.
- Sandboxing: as its name, you can freely make and changes in you code and test it in your own computer before "checking in" what you have done.
- Branching and merging: you can made your own copy of the code, save it in a separate location and develop it in isolation. Later, you can merge your work back into the common area.
The common words you have to know
There are many implementation of a VCS, but all of them should involve these concepts:
The basic:
- Repository: the database storing files
- Server: the computer has the repository
- Client: the computer connect to the server to use the repository. The server and the client may be the same computer.
- Trunk/Main: the primary location for your code. It is considered as the main branch of your work.
Basic actions:
- Add: put a file (and/or a directory) into the repository in the first time.
- Revision: the version of a file. It can be a number-liked string as 1, 2, 3, … or 1.2, 1.3, …
- Head: the latest revision in the repository.
- Checkout: download files from the repo to your local computer. Some VCS allow you edit the files when they were checked out, others require a explicit option when checking out, otherwise they only give you a read only version.
- Check in: upload files to the repository. If the file exists and have changes, it will have a greater revision number. You can leave a message when checking in.
- Changelog/History: a list of changes to a file from the time it's added to the repository.
- Update/Sync: ynchronize you files to the latest version (head version) of the repository.
- Revert: throw away your local changes and roll back to the latest verion from the repo.
Advanced actions:
- Branch: create a separate copy of your work. It is also a noun refers to the working copy which is branched.
- Diff/Change/Delta: find the differences between two files.
- Merge/Patch: apply changes from a file to another, for example, aplly what you did in you branch to the common work.
- Conflict: when there are some changes which cannot be applied in a files in the same time, you know that there is a conflict.
- Locking: make some files not allow other people to edit it. This is usually used to prevent conflict. You can unlock it later. Some person can unlock the files on purpose when needed, which is called breaking the lock.
Thanks to Kalid Azad at https://betterexplained.com for this section.
Back to the real world, which tools you can use
After reading all above, you can wonder how to use a VCS, implement your own? Feel free to try, but there are many free tool can help you. SVN (subversion https://subversion.tigris.org) and GIT (https://git-scm.com) are two of them. If you are working in Linux or some console system, just get these software to your computer and you the console! For windows users, TurtoiseSVN and TurtoiseGIT (found at https://tortoisesvn.tigris.org and https://code.google.com/p/tortoisegit/) can be a great choice.


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Though there is still one game to play, our bar challenge is over, since nobody picked Butler or Duke to be in the final game. So the final standings are the same as the ones we put up several days ago:
John R 2: 242
Aaron: 227
Sean: 215
John R 1: 213
Mike C: 212
Ray: 175
Malcolm: 166
Jon Stan: 142
Glynn S: 140
Mike H: 115
Evan S: 91
Thanks to all for playing.
Monday, April 5, 2010
NCAA Tournament Challenge final standings.
Posted by J-C. G. Rauschenberg at 2:09 PM
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How Substantial Listens To Music
Aug 29, 2011 • substantial
Push past the big metal door at Substantial and you're going to hear music. Maybe it's a some dream pop from Beach House or maybe it's some slowly thumping Mark E or some classic David Bowie or Talking Heads. Exactly how do we create that experience? We've been asked a few times about this so we figured we'd lay it out for you in case your own office needs some help.
As far as hardware goes, there are three pieces that make everything work. We've got a stereo, an AirTunes, and an iMac that we lovingly refer to as The Infinite Jukebox. The stereo's place in this is obvious. We set up the AirTunes on one of the auxiliary inputs and anyone can share their music with the office. That used to be the primary way of doing things until The Infinite Jukebox arrived, at which point more network-centric software took over, with the quartet of iTunes, Rdio, and Spotify and SoundCloud as our go-to tools. None of them quite do everything we want, so we use them all to keep the music going. Here are details on how we use each.
iTunes is our veteran office music provider; we've already mentioned using it as proxy for Airtunes, but with The Infinite Jukebox we've shifted to shared libraries. It's as simple as browsing someone else's library (or the music local to the machine) and playing what you want. It's a system that's always worked well, but even with our vast collections we don't have everything. That's where the cloud-based services come in.
Rdio is young but it's already become a core part of our regular music-listening experience. The web application has a beautiful interface and is truly a joy to use. Plus there are no software updates. It's got lots of tracks and the social features are neat even if we don't use them to any degree. We've been using them since before Spotify's US launch and haven't stopped. It's not perfect (close the wrong browser window and there goes the music), but it works.
Spotify's recent foray into our hearts and headphones is simple to explain. They have a lot of songs. 13 million of them. That gets us a lot of Grace Jones (or anyone else for that matter). Shared playsits are fun, but the clunky methods to actually using them is a bit frustrating (Spotify, why should we have to search Google to find playlists for your app?). The interface is achingly similar to iTunes, which made this one incredibly familiar to use even on the first try.
You might be less familiar with SoundCloud, as it's a service used mostly by electronic music producers. It's not too dissimilar from Bandcamp (minus the retail aspect), allowing artists to upload their wares for streaming. Because of the audience, there are a lot of DJ sets posted to the service as well, providing a source for all manner of beat-centric fare.
And there you have it. Listening to music at Substantial is an all day, everyday thing, and we're always on the lookout for something else to help let the music play on. Next up is this installation of our permanent DJ booth. Things are definitely going to get a bit louder around here.
Image from cpgmattr.


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Welcome to my blog!
Tuesday, May 17, 2016
Snow Globe card
23 comments:
- Cindy C. said...
Oh my this is wonderful!! Such a cute wintery scene in a snow globe!!!
- May 17, 2016 at 10:09 AM
- Barb said...
Oh, Linda, this is stunning! Just LOVE IT!!!
- May 17, 2016 at 11:05 AM
- Betty Keefe said...
that is so cool Linda - looks like a winner to me - and congrats on your HM from last week's challenge!
- May 17, 2016 at 5:40 PM
- Bonnie said...
I like that some of the sequins stick to the deer! That's the case with a real snow globe so it works perfectly in my book! What an awesome card, Linda! Thanks for sharing it with us at Merry Monday!
- May 17, 2016 at 6:29 PM
- Pam Sparks said...
So pretty Linda! I love your globe!
- May 17, 2016 at 9:43 PM
- Karen D said...
I love how your globe turned out Linda. It looks like a real snow globe....'Mid shake' Perfect.
- May 17, 2016 at 10:03 PM
- Lin said...
Ding, ding, ding.......I think I see a winner here! Perfection!
- May 18, 2016 at 1:48 AM
- Linda said...
Beautiful snow globe card, Linda. Love the glittery look. Thanks for joining us this week at Merry Monday.
- May 18, 2016 at 10:58 AM
- Notes by Nina said...
Stunning snow globe card Linda, I love all that shimmer. Thank you for joining us for Merry Monday.
- May 18, 2016 at 2:15 PM
- Cat Craig said...
oh wow Linda, you out did your self! This is hands down the most gorgeous globe type card i have seen.
- May 18, 2016 at 6:22 PM
- Greta said...
Beautiful scene, Linda--love your creativity!
- May 18, 2016 at 11:41 PM
- Virginia Lu said...
Absolutely gorgeous and enchanting! Love the shaker element in this snow globe! Beautifully done, Linda! Hope you are enjoying retirement! Hugs!
- May 19, 2016 at 12:35 PM
- Colleen said...
Beautiful and peaceful scene Linda!! So glad you played along at Merry Monday again! Always great to see you in the gallery!!
- May 19, 2016 at 1:20 PM
- Cheryl W said...
Stunning card!
- May 19, 2016 at 5:46 PM
- Marcia HIll said...
Oh my...this is just over the top fabulous Linda! I love that the card is in the shape of a snow globe, and I really, really love the white and glittery scene in the snow globe! Beautiful, beautiful card!! :0)
- May 19, 2016 at 6:35 PM
- fabiola jaques said...
- May 20, 2016 at 1:23 PM
- KimCreate said...
You have fabulous cutting skills with the silouette! This card is stunning!
- May 21, 2016 at 8:41 AM
BEAUTIFUL!! Linda, this snow globe looks so REAL!!!
- May 21, 2016 at 7:10 PM
- Susan Joyce said...
Awesome design, love all the glitter inside the globe. Thanks for sharing at Merry Monday.
- May 21, 2016 at 10:49 PM
- Lizzie T a/k/a Wifelady said...
This is stunning! I love that everything in the snow globe is white - some simple but gorgeous! Amazing job!
- May 22, 2016 at 10:46 AM
- Andrea La Vigne said...
This is so cool (no pun intended)! Love all the glitter, and the fact you made it a shaker card. Tfs!
Andrea's Paper Antics
- May 22, 2016 at 11:47 AM
- conil said...
Absolutely magical and a perfect depiction of what a snowglobe should be. All sparkly, clear and fun to shake.
- May 22, 2016 at 12:36 PM
- Greta said...
Well-deserved HM at MM--congrats, Linda!
- May 23, 2016 at 10:28 AM


text: Niloo graduated from OCAD University in 2015 with a bachelor of fine arts. Her artistic practice focuses on human relations and examines how they are defined through identity, emotions, and varieties of human impressions. Since graduation, Niloo has participated in several group shows and art fairs in Toronto. She currently lives and works in Toronto, Canada.


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Barbara Jean Binder
Barbara Jean (Smithers) Binder, 47, of Oshkosh died Thursday, March 7, 2013, at her home after a courageous battle with colon cancer. She was born Dec. 30, 1965, in Fond du lac to John and Susan (Calhoun) Smithers. On July 1, 1988, she married David Binder at the Holy Angels Catholic Church in West Bend.
Barbara was a loving and devoted mother and wife, who always put her family first. She will always be remembered for her beautiful smile, infectious laugh and her love of cats. Barbara most recently worked in the credit department at Jansport.
She is survived by her husband, David of Oshkosh; her children, Stephanie and Andrew Binder of Oshkosh; her parents, John and Susan Smithers of West Bend; and her brother, David (Ruth) Smithers of Racine and her sister, Mary (Brian) Ogle of West Bend.
The family would like to extend a special thanks to the amazing staff at the Aurora Vince Lombardi Cancer Clinic as well as the Visiting Nurse Association for the loving care they provided in the past eighteen months.
Funeral services for Barbara will be Monday, March 11, 2013, at 6 p.m. in the Poklasny Funeral Home, Oshkosh, the Rev. Matt Simonar officiating. The gathering for visitation will be at the funeral home, 870 W. South Park Ave., on Monday from 4 p.m. until the time of services. Burial will be in the Sacred Heart Cemetery.
In lieu of flowers, a memorial has been established to the American Cancer Society.


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These nails were inspired by those famous pink and red stripes on the VS shopping bag (click photo to enlarge). I threw in some gold in there to represent the gold VS logo printed on the bag. When looking for nail art ideas, just look around. You might be inspired by the pattern on your favorite dress, the colors on your sneakers, or um… a shopping bag. Doesn't take much to inspire me!
Monthly Archives: April 2012
DIY: The Statement Pillow
I had a few people asking me about the 20 X 20 "Go To The Gym" felt pillow on my bed in the sausage ponytail tutorial video, and I am proud to say that it was made by yours truly! I saw a similar pillow on Etsy that was $100, and I was determined to copy it. My broken sewing machine has been stuffed away in a closet somewhere for years, so I stitched the whole darn thing by hand. It was actually easier that I thought, only taking a couple hours. I ended up making the "let's make out" pillow the next day with the leftover felt.
To follow the same basic pillow tutorial that I used, click here. To make the letters, I cut them out of paper first, then I placed the paper letters wrong-side-up on the felt and traced around them with a sharpie. That way when you cut them out, the marker will be on the underside of the felt letter. I hand sewed the letters onto the pillow, but you could easily just glue them on with fabric adhesive. If you have an old throw pillow that you no longer use, you could just cover it, or take the filling out to stuff your new cool pillow. Have fun!
NOTD: The Starfish
Continuing with the whole starfish theme, here are the nails to go with your DIY headband! I started to get a little starfish-sloppy with these, but they still turned out pretty sweet if you're not too critical. Use little paint brushes and/or homemade dotting tools (pencil, bobby pin, or sewing pin tips) to create the details. Have a great week everyone!


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Vintage teals and marigolds combine to form this bohemian duvet cover with an eye-catching floral pattern sure to make your bedroom design pop.
Hand-sewn and meticulously handcrafted, this boho-chic duvet's heavyweight construction is designed for maximum comfort and wrinkle resistance. Plus, it comes with hidden zipper and comforter ties.
• Hand made: Cut, stitched & sewn by hand • Fabric: (See tab just below) • Extra wear resistant • Inside comforter ties • Hidden zipper • Available sizes: Twin, Queen and King • Machine wash cold with gentle detergent • Comforter insert not included • Shams sold separately • Estimated shipping: 5 - 10 days • Made in the USA
• Twin: 68"W X 88"H • Queen: 88"W X 88"H • King: 104"W X 88"H
Brushed Poplin
Our brushed poplin blend is midweight and extra breathable. Extremely wear and wrinkle resistant, but ultra soft to the touch – the brushed poly-blend won't pill, shrink or fade. Machine wash cold on gentle cycle with mild detergent.


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Bipin Shah, Chairman and CEO
Bipin Shah has been a veteran of Silicon Valley for over 3 decades and has worked both in the Semiconductor and Software domains. He has been VP of Global Operations for Altera – a major PLD- FPGA company – recently acquired by Intel, where he helped operationally grow the company from zero to over $500M in revenue over 11 years. He was then named President of Altera Japan where he grew Altera's business in Japan from $55M to $120M in less than 3 years.
Prior to that he started his chip career at Fairchild where over a period of 11 year he held positions in Engineering, Quality and Reliability and Manufacturing Management.
His software career started with Kovair where since early 2005 he has transformed the company into an Integrated ALM solutions provider and a leading provider of integrations for major third party development and other tools with Kovair's trademark Omnibus Integration Platform.
Bipin holds a BEE (Hons) in Electrical Engineering from Jadavpur University, Kolkata and a MSEE from University of Wisconsin, Madison.
Amit Dasgupta, Director, Major Accounts and Partnerships
Until his assignment to the current role, Amit Dasgupta headed Kovair's Marketing efforts and brings with him expertise in Application Lifecycle Management (ALM), SDLC and PPM domains spanning over 18 years. He started as an Application Developer with focus in developing client/server and web related products in Microsoft .Net platform. Currently, he strategizes on the growth, market direction, and customer engagements for Kovair's exclusive range of ALM and Integration products. Until his recent assignment he has held the responsibility of defining new products and marketing plans for them.
Amit holds a Bachelor's degree in Mathematics Honors from Calcutta University and a Project Management certification from PMI Institute.
Joydeep Datta, Director, Product Development
Joydeep Datta has over 15 years' experience in distributed Web Services, Enterprise systems using various distributed technologies. He has more than a decade of experience in managing the entire lifecycle of product engineering for mid-to-large scale business integration solutions. Joydeep's recent technology focus has been on UDP, Compression and the Binary Encoder and Web Sockets. He has successfully architected multi-tier distributed ESB platform for large scale, high-volume integration system. He is passionate about building teams, products, technology and great engineering culture for massively scaling businesses.
Joydeep received a pure science degree from Burdwan University in West Bengal. He has also been awarded with GNIIT Excellence in Software System Management.
Rajib Akhter, Sr. Director, Business Development, US
Rajib has over 15 years of experience in sales and marketing. At Kovair Software, he has secured business form several marquee customers. In a direct reporting relationship with the CEO, he strategizes with him and executes at the account level to win the business.
Earlier he co-founded several software companies in the San Francisco Bay area. Yubé in Customer Relationship Management, Ohana Health in healthcare and WebScalers in Search technology. He was responsible for overall company strategy including sales, marketing, IT, customer services, and raised venture and government funding for them. He also secured their solution / technology partners and resellers. He was a founding employee at Actuate Corporation (NASDAQ: BIRT; acquired later by OpenText, NASDQ: OTEXT). He started and grew their customer support and consulting services team: generating 8% of the company's total revenue.
Rajib holds an M.S. in Electrical Engineering and Computer Science from University of Hawai'i and a B.S. in Electrical and Electronics Engineering from Bangladesh University of Engineering and Technology (BUET).


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Investment strategies of corporate venture capital in life science industry revealed
Press releases • Dec 14, 2011 09:34 UTC
The US continues to dominate; most venture capital goes to drug discovery platforms and the most successful companies in need of venture capital are those who most clearly fit in to investors' strategy. Despite a leading R&D position, Swedish life science companies must improve international relations to succeed in attracting investments. This emerged in a new report on corporate venture capital.