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26.06.2014 Kuopio hosts the WHO European Healthy Cities Conference next summer
Kuopio has been chosen for the host city of the WHO European Healthy Cites Conference in summer 2015. Read more ›
Healthy growth and planned development are the signs of a successful business.
Operational development, expansion into new markets and implementation of vision is enabled through teams and clear, well-planned activities.
Operational development involves actively seeking and exploiting new opportunities.
In order to gain new ground, you need to establish a route and proceed at the optimal pace.
You never know what the next decisive competitive advantage or recipe to success is.
Kuopio has been chosen for the host city of the WHO European Healthy Cites Conference in summer 2015. Read more ›
The International 22nd Puijo Symposium is held in Kuopio. This years theme is Physical exercise in medical medicine - critical appraisal of scientific evidence. Read more ›
Runway, Commercialisation runway of innovations -project has been chosen as the only Finnish candidate to represent Finland in the European Enterprise Promotion Awards -competition, which is organised by the European Commission. Read more ›
Games for Health Finland Game Jam combined health and wellbeing technologies as game controllers and incubated new out-of-the-box game ideas for health promotion with 50 devoted jammers in Kuopio, Finland, April 25th to 27th. Read more ›
"We don't see things as they are, we see them as we are" game theme gathered 23 293 game developers from 72 countries together to make games in 48 hours during the world's biggest game event Global Game Jam 2014. Read more ›
Nutrition-related health games are still relatively new area in health games and have expectance of high growth in the near future. The next few years will therefore show us what nutrition games will bring, but still it is clear that they have a great potential in health promotion.
In the autumn 2013 Mega Electronics participated in an event called "Game Jam" which was held in Kuopio during Finland's first Games for Health event.


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NARS is releasing an all new Matte Multiple collection! The multiples are great because they're multipurpose and you can use them on the eyes, cheeks, or lips. I usually prefer cheeks and eyes.
NARS says
NARS brings vibrant pops of color and sensual sun-kissed hues to lips and cheeks with the new Matte Multiple.
Founder and Creative Director François Nars takes one of the brand's most innovative and iconic products and adds a modern twist on the cult classic.
Available in seven shades from ginger pink to golden bronze, the Matte Multiple features a creamy, lightweight formula that delivers buildable, long-lasting, hydrating color for lips and cheeks. This innovative formula can be applied dry for a soft yet vibrant matte effect or wet for a rich and vivid finish that melts into skin.
Available March 1, 2014 at NARS boutiques and on narscosmetics.com.
Altai – rose bronze
Anguilla – ginger pink
Cappadoce – golden bronze
Exumas – pink apricot
Laos – rose coral
Siam – poppy red
Vientiane – copper bronze
The shades that excite me the most are Anguilla and Altai. What do you think of the new Matte Multiples?
Tags: NARS
OOOOO I love this!!! I am a huge fan of cream type blushers and lip-to-cheeks! Oh man I am so excited for this now :)!! I have been looking for a bronzie type cream blush and Altai seems perfect!
Thanks for sharing!!

subset: commoncrawl


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To me, the saddest food is probably the hot dog at Hooters, its grossly overstated "gourmet" billing somehow adding even more pathos and disappointment to the life of a desperate-for-female-interaction middle-aged-man whose spirits sink even lower when he sees this fraudulent entree delivered to his high-table-for-one by a server who can't entirely disguise the pity in her eyes. Or perhaps it's the soggy, slug-textured peanut-butter-and-jelly sandwich discarded with disgust by a 3rd grader whose mom overloaded it with extra grape jelly in a misguided attempt to please the distant child she's never quite been able to reach. The SA Forum Goons came up with lots of additional suggestions, and they're not so much traditionally ha-ha funny as they are deeply depressing. But when read as a whole, this menu takes on a tragicomic tone, and tragicomedy is a kind of comedy. Bon appétit!
Thanksgiving dinner for one.
No food is sadder than ikizukuri.
It is shredded wheat. Not frosted. A big block of it in a plain white bowl, half full of milk. It is on a table, where a man sits. There is no other food on the table.
The man is dressed in a white shirt and black slacks, and he'll put on a tie when he's finished. Maybe he's not alone, it's just very early and his family is still asleep. He takes his spoon and turns the block of shredded wheat over in its bowl, so that the other side can soak. He feels his hunger, but he waits anyway. After a period of time, of a length roughly the same as yesterday, and the day before (this time-period has become instinctual for him), he picks up his spoon and begins to break the block up. Not completely of course, just into chunks that fit squarely onto the spoon. The chunks usually have one side that's soggy and one side that's still a little bit crunchy. The way he spoons each into his mouth, along with an appropriate quantity of milk, puts the crunchy side at his teeth and the soggy side on his tongue.
As he chews, the crunchy side gets pulverized while the soggy side is mashed up by the natural motion of the tongue while chewing. When he has eaten all the chunks, there is still milk left in the bowl, and in it the crumbs that resulted from breaking the initial block. He does not raise the bowl to his lips to drink the remainder; even though no one is there to see, he sticks to his etiquette and dutifully drains the bowl spoonful by spoonful. When he is finished, there are still crumbs in the bowl. He gets up from the table, takes the bowl to the sink, and quickly rinses it out. He leaves the bowl in the sink; it will be dealt with later. He walks away to get his things, and then he leaves. The sun has not yet risen.
Flavor Bear
The saddest food is when you have exactly one dollar for dinner so you buy two small apples and take them for your dinner at work in the porno store. Then during your shift you notice a customer left their Subway steak sub behind, and it is still warm and untouched. So you get really excited that you don't have to eat just two apples for dinner and eat the sub. This happened to me.
Tshirt Ninja
The saddest food is Ensure in a measured cup under the hawk-like supervision of unpleasant eating-disorder psychiatric ward staff in a fluorescent hospital cafeteria full of human skeletons.
There's something about mashed potatoes. I like mashed potatoes but it's gotta be the least passionate food ever. It's so bland and neutral.
Ferguson's long arm of the law laments the latest cutback.
Simply put, if I had Johnny Manziel's physical gifts, you better believe I would be there in the Weight Room, getting to bed early, doing whatever I had to do to be the best possible athlete I could be. I wouldn't be posting on social media about sucking titties. I wouldn't even look at a titty, buddy. I'd look at a titty and see two big footballs.
Can you read books at work? Can you watch porn there? Is THAT what I think it is? Yeah, probably NWS
Former Bears coach Mike Ditka has opinions about more than just the Redskins name.
Dogs hate water. That's because dogs know better than us what's healthy. They're closer to nature.
The Comedy Goldmine examines the funniest and most creative threads from the Something Awful Forums. Although the Comedy Goldmine has changed authors many times over the years, its focus on the Something Awful Forums is still the same. Includes hilarious Photoshops, amusing work stories, parodies, and other types of oddball humor.
Copyright ©2014 Rich "Lowtax" Kyanka & Something Awful LLC.


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Rated 5 out of 5Â by 1 reviewer.
Women Studio Apparel
Shapewear Hero 2.0 Capri
Black (Z86431)
Size Chart
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Rated 5 out of 5Â by kiakia Makes legs/ butt look awesome! I really love these crops. They are a thicker material and are very much a compression pant. I am 162#, 5ft 7in tall, my hips are roughly 43in and wiast is about 34.5in. I bought a medium. They fit tight but no muffin top, no pulling up while working out. I feel nice and snug in these. Nothing jiggles :). Best thing is they slim and trim you. Fake it 'til you make it! lol Great buy! 7/7/14
1-1 of 1


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'Big Brother' season 16, episode 28 recap: Sting of the scorpion
Mark Gatiss returns to 'Game of Thrones'
Sanrio reveals Hello Kitty is not a cat
First look: Father Gabriel in 'The Walking Dead' season 5
'AHS: Freak Show' poster revealed
Why was Vin Diesel cast as Groot in 'Guardians'?
'The One I Love' star Mark Duplass, director Charlie McDowell talk secrets, alternate storylines
The 10 best 'Emma Approved' episodes
The craziest outfits on the VMA red carpet
'Doctor Who's' WhoHype podcast is live today at 2:30
'Teen Wolf's' Ryan Kelley is 'in the dark' about Parrish's abilities
'The Art of John Alvin'
'If I Stay'
'Toy Story of Terror!' DVD/Blu-ray
'The Giver'
Seven Disney Classics DVD/Blu-ray
Episode #78 – Double Stuf Murder
Episode #54 – Talking Memoirs with Paige Rawl
Episode #22 – Deep Breath
Episode #70 – 'Avatar: The Last Airbender' – 1×09, 1×10 – Grand Theft Avatar
Episode #235 – The Great Demotion
Sign up for a free account with Hypable. This lets you personalize your news feed and write your own articles.
Posted on 15 Oct, 2012 in Downton Abbey


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Electronic Publishing Expo
Mr. Potash explained the benefits electronic books and how to use them. Mr. Hutton talked about technology for protecting… read more
Mr. Potash explained the benefits electronic books and how to use them. Mr. Hutton talked about technology for protecting copyrights. Ms. Hall talked about their online reading site. Mr. Thomas talked about a distribution system for electronic books. Ms. Peterson talked about printing books on demand from digital files. close
People in this video
- Hall, Melissa Director of Marketing BookFace Technologies
- Hutton, Les Vice President ContentGuard->Marketing
- Peterson, Susan Vice President Lightning Source->Marketing
- Potash, Steve President and CEO OverDrive, Inc.
- Thomas, Thomas Chairman 10N Systems, Inc.
Hosting Organization
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All good things come to an end
This will be my final post. I want to thank all of my followers. I sincerely hope you have learned from our experience as part of the National Demonstration Project. It is hard to believe that the study has been finished for nearly three years! It was one of the first patient-centered medical home (PCMH) pilots in the country. We learned from this process that transformation is difficult. Change management is a skill that can be learned, but requires personal transformation on the part of the manager and the physician. We learned that transformation is an ongoing process that never truly reaches a finishing point. We learned that initial transformation into a PCMH takes much longer than two years.
Today, there are more than 100 PCMH pilots in the country; some complete, some ongoing. Results confirm the notion that the PCMH-way of providing medical care delivers. Patients and providers love it. Quality numbers are better. Outcomes are better. Practice and patient finances are better. Perhaps the most exciting pilots are those in the residency programs. It will be exciting to see results of those studies. See TransforMed's P4P for such a program.
I encourage all readers to continue on their journey toward building a PCMH. If you are interested enough to seek out information, you are likely very deep in creating your own PCMH. I hope you all keep in contact with wonderful resources like Family Practice Management, AAFP, Patient-Centered Primary Care Collaborative (PCPCC) and Delta Exchange. I hope to meet many of you as I continue my journey into the future of family medicine.
–Melissa Gerdes, MD
Posted at 10:34AM Mar 22, 2011 by Lynn Hofeldt | Comments[2]
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Sign up for Yardbarker's daily Top 10 newsletter, the Morning Bark! Customize to get news on your favorite sports and teams.
Found April 26, 2013 on Pro Football Zone:
PLAYERS: Aaron Rodgers
TEAMS: Green Bay Packers
TEAMS: Green Bay Packers
According to Tom Silverstein of the Milwaukee Journal-Sentinel, Aaron Rodgers' contract extension with the Packers is worth $110 million over five years. That's an average of $22 million per season. Rodgers deal with #Packers is five years, $110 million, highest salary in NFL history. — tom silverstein (@TomSilverstein) April 26, 2013 Rodgers; guaranteed money is astonishing. Aaron Rodgers new contract: 5 years, $110M. That's $22M per. $40M in the first year (wow). Over $62M in the first three years. — Ian Rapoport (@RapSheet) April 26, 2013 Need NFL Tickets? The post Aaron Rodgers' contract is for five-years, $110 million appeared first on Pro Football Zone.
Original Story: http://feedproxy.google.com/~r/ProFoo...
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By: Jenn Schanz
The victim, who doesn't want to be identified, says she was surprised to come face to face with the burglar, who was standing right outside her bedroom.
"I came in my house and saw that things were...that things were missing. So I assumed that they were already gone, and then he came out [of] one of the bedrooms and I was like...he's still in my house," she says.
The victim yelled at the burglar to get out of her house, and he quickly took off running with two laptops, a duffle bag, and some cigarettes.
The victim describes the suspect as a black male in his late twenties.
He's bald, around six feet tall, with a medium build.
Neighbors nearby heard the woman yelling, and came outside to check things out. Because she wasn't home, the woman says she's not surprised her house was targeted.
"If your house looks like...if there's not a car there and the windows might be pulled, people just think you're not home."
The victim says Tuesday's trauma has taught her the importance of getting to know your neighbors, so that you can look out for each other.
"Any time of the day, it could be in the morning, it could be at night. If you see somebody that you know, your neighbors, aren't home, just look out for them maybe."
The burglary is still under investigation.
Police say they're reviewing footage from a neighbor's security camera in hopes of finding the suspect.
Anyone with information in urged to call CrimeStoppers at 402-475–3600.
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Rating Feedback for Dr. FINE (2552409)
The rating:
'Horrible doesn't stand behind his work if a problem arises. His wife is the staff she holds hush balls in her hands literally she makes the prices he isn't a good dentist like aI originally thought. Karma has it's way of coming back around.'
We're sorry that this patient felt that way about their visit. At our practice we offer a very high standard of care, but we believe taking care of your teeth is very important to your general well-being and your overall health and so we try to fully inform our patients as to their needs. We do hope this patient finds a dental practice that they love and go to regularly, because that is whats most important.


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We stayed here for one night. It is located in a suburb of Ljubljana about 25 minutes walk from the centre, mostly along quite a busy road. Our room was very small, so much so that it was hard to find anywhere to open the suitcases, but adequate and comfortable. We ate in the restaurant - a good value buffet... More
- Reservation Options:
- TripAdvisor is proud to partner with Hotels.com, Booking.com, Priceline, Expedia, Travelocity, Orbitz, Tingo, Otel, BookingOdigeoWL, HostelBookers, Hotel.de and Venere so you can book your M Hotel reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- m Hotel Ljubljana


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Showing results 40398-40437 of 50067
PRESS RELEASE: Virgin Comics Launches "Guy Ritchie's Gamekeeper
WWLA: Schmidt talks "Avengers Classic"
This June, Marvel Comics will give fans something old, something new, and something red, white and blue with release of "Avengers Classic" #1. We spoke with Editor Andy Schmidt about the series.
PRESS RELEASE: "XIII Vol.1: The Day of the Black Sun" Scores With American Readers
Stan Lee Inc vs Marvel? Read On True Believer...
Marvel Comics has refuted claims in a lawsuit filed by Stan Lee Media Inc, who have also found their claims in dispute by Stan Lee himself. Confused? Read on.
PRESS RELEASE: "Mighty Avengers #1" Sells Outs
Loeb talks "Fallen Son: The Death of Captain America"
Following the death of Captain America, the Marvel U is mourning the loss of one of their greatest heroes. Jeph Loeb will examine that grief in the upcoming "Fallen Son: The Death of Captain America."
Comic Book Urban Legends Revealed #94
Those crazy guys at CSBG are back with more truth than even Colbert could handle! Was Cap supposed to die before? Does Jonah Hex look like someone you know? All that and more-- just click on the link.
Spider-Man 4, Heroes, TMNT, Transformers: March 16th Comic Reel Wrap
Mary Jane says, "Not without my Raimi!" Also a look at the next ep of the NBC series, new videos from the sewers, new photos of Robots in Disguise, plus Jim Rhodes, Victor Von Doom, Hellboy, and more.
Preview: "Degrassi: Extra Credit" Volume 4
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"Okko" - Japanese-Style Demon Hunting By Way of France
Need a ghost and demon hunter? Who you gonna call? How about Archaia's "Okko?" We spoke with French creator Hub about this uniquely told and designed series.
Downloading the Cow: Hawkins talks Downloadable Comics
Top Cow President Matt Hawkins sat down with CBR News to discuss the studio's plans for downloadable comics version of books like "Witchblade" & "The Darkness."
Image Previews: "The Walking Dead," "Godland" and More
"The Walking Dead" #36 and "After The Cape" #1 are just some of the Image Comics previews we've got for you today. Check out the new issues of "Girls" and "Gødland" too!
Spider-Man 3, Speed Racer, Whiteout, Transformers: March 15th Comic Reel Wrap
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"Spider-Man 3" VG Subterranean Featurette
In addition to miles and miles of Manhattan sky line, the upcoming "Spider-Man 3" video game features over 20 miles of subways and sewers and we've got a video preview for you.
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PRESS RELEASE: Aspen MLT Set To Launch A New Series And More At Wizard World Los Angeles
PRESS RELEASE: Platinum Studios Makes A Show at Wizard World Los Angeles
PRESS RELEASE: Veritas Games Company Releases Comic Book Card Game Featuring Top Cow Characters!
PRESS RELEASE: "Punks" Invade Wizard World LA
STUDIO TOURS: Artist Jock
"The Losers" and "Green Arrow: Year One" artist Jock invited CBR News to his England studio for a detailed tour of his studio, and we've brought back tons of pictures.
MARVEL PREVIEWS: "Runaways" #25, "Avengers: The Initiative" #1 and More
Marvel Comics previews some of its most hotly anticipated titles for April, including a five-page advance look at "Runaways" #25, the first issue by Joss Whedon.
PRESS RELEASE: Image's "Dynamo 5" #1 Sells Out, Back To Press
The new Image Comics series "Dynamo 5" by Jay Faerber has sold out and is going back for a second printing.
Warren Ellis Starts A Revolution In "Black Summer"
Learn why your definition of a hero may be put to the challenge this June, with a new superhero epic by Warren Ellis and Avatar Press. We spoke with Ellis about "Black Summer."
"300" Post-Game: One-On-One with Zack Snyder
With "300" shattering records this past weekend, CBR's Jonah Weiland spoke with director Zack Snyder for a post game report and to see where things stand on "Watchmen" (casting rumors, that test shot, designs & more).
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PRESS RELEASE: "Dynamo 5" #1 Second Printing Announced
PRESS RELEASE: Eric Shanowar Brings "Age of Bronze" To Life
PREVIEW: "Witchblade Manga" #2
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TMNT, Transformers, Iron Man, The Man of Steel: March 14th Comic Reel Wrap
There's heroic amphibians all over the place, and giant robots too. One of Stark's nemesis is revealed, Clark Kent gets held over, plus news on "Heroes," "Hellboy," "Spider-Man 3" and more.
VIDEO: "TMNT" Featurette With New Scenes
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PRESS RELEASE: Oni Races into "Space"
This April, Oni Press will join the space race by releasing the all new original graphic novel FIRST IN SPACE by talented newcomer James Vining, winner of a 2006 Xeric Award.
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PRESS RELEASE: The Hero Initiative Rocks Wizard World Los Angeles With Mike Perkins!
Other Booth Events Include Campbell, Gossett and Mayhew Signings and Ebay Lunch And Sketch With Perkins and Gage!
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PRESS RELEASE: DC Comics Remembers Writer Arnold Drake
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Archives: All | Comic Books | TV/Film | Video Games | Web Comics


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Great Views from this Oceanside 3Br Duplex in Wrightsville Beach
- bedrooms 3
- baths 2½
- sleeps 6
- pool no
- hot tub no
- pets considered no
- type House
rates (USD)
/ night
$ 1,620 - $ 2,200 / week
vacation rental description
Attractively decorated 3 bedroom 2.5 bath lower duplex just one house back from the beach with great views of the ocean from the covered porch, complete with comfortable seating. One-level floor plan features an open living-dining and kitchen area opening onto the covered porch. Perfect for entertaining! A game area with wet bar is a special get-away spot off the ground level foyer for teens and adults alike with Wii, Xbox 360, Play St. 3, wet bar, ice machine, small refrigerator and TV. The garage has been transformed into another game room with 9 game Foosball Table, Chess/Checkers Table , and pool table. With all this to do, you may not want to leave the home! If you do, the beach access and Johnnie Mercer's Pier are just steps away! Enclosed out-side shower. Parking for 3 cars in driveway. Occupancy: 7. No Smoking. No Pets.
property availability
- dates with deals
- unavailable dates
Last modified on 09-1-2014 at 9:53 AM.
email owner view full calendar
Bryant Real Estate 910 256-3764
house rental amenities
Property Type
- house
- washing machine
- clothes dryer
- ceiling fans
- air conditioning
- internet
- iron & board
- kitchenette
- dishwasher
- refrigerator
- microwave
- ice maker
- coffee maker
- toaster
- dishes & utensils
- wet bar
- Bathrooms
- 2 bathrooms 1 half Bath
- Bedrooms
- 3 bedrooms, sleeps 6
- foosball
- games
- pool table
- dvd player
- satellite / cable
- vcr
- cd player
- outdoor grill
- golf
- lanai / gazebo
- balcony
- pets not allowed
- non smoking only
payment methods
Owner has not provided their accepted payment methods
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text:
Make the Strip District a safer place for pedestrians
"We, the concerned residents of Allegheny County, petition the city to make the strip district a safer place for pedestrians. Over the past 6 months, numerous people have been hit by reckless drivers speeding through the busiest streets of the Strip District (Smallman Street, Penn Avenue, and Liberty Avenue). We as taxpaying citizens should not have to worry about risking our lives to cross the street to go to work. Some type of traffic control needs to be implemented immediately on each and every one of these roads, before another innocent victim gets hurts or dies."
No comments yet.join the discussion
Recent signatures
Kelli OrlandoUnited States3 years ago
Adam ReepUnited States3 years ago
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text:
Muskego - Seventy-four students at Muskego High School last year earned advanced placement awards in recognition of their exceptional achievement on exams in their college level courses at the end of last year.
High schools offer AP college-level courses in conjunction with the College Board. To attain college credit, students must pass an exam at the end of the year.
Only about 18 percent of the top 1.6 million students worldwide who took AP exams performed at a sufficiently high level to also earn an AP scholar award from the College Board.
The College Board recognizes several levels of achievement.
Six Muskego High School students were honored with the National AP Scholar Award by earning an average score of at least 4 on a 5-point scale on all the AP exams they took. The minimum number of exams was eight.
Achieving the National AP Scholar Award were Alex Hanna, Ryan Johnson-Evers, Nicholas Klinka, Sebastian Miller, Nicholas Spoerk and Jacob Varsos.
Twenty-three students qualified for the AP Scholar with Distinction Award by earning an average of at least 3.5 on all AP exams they took. Honored were Aaron Beczkiewicz, Joseph Blommel, Taylor Cesarz, Kristen Furry, Alex Hanna, Ryan Johnson-Evers, Kyle Kaja, Kaitlyn Kamperschroer, Nicholas Klinka, Jiaqi Li, Paige Liberski, Ashley Manske, Rachel Matson, Sebastian Miller, Samuel Owen, Jared Pradarelli, Keighley Reisenauer, Michelle Roubik, Jon Scott, Nicholas Spoerk, Ana Spone, Jacob Varsos and Lauren Wundrock.
Twenty-one students qualified for the AP Scholar with Honor Award by earning an average score of at least 3.25 on all AP exams. They were Graham Ambrose, Amanda Bourbonais, Tyler Dotzler, Joseph Egan, Kayla Farner, Alexander Feuling, Katelyn Gehrke, Maxwell Goebl, Rebecca Horwath, Paul Hurlbut, Alex Kocher, Margaret Ludwig, Melissa Mason, Kylie Reese, Megan Rogahn, Abigail Schilz, Christina Tersine, Nicholas Tretow, Alexander Wallner, Rachel Wegener and Lauren Williquette.
Thirty students qualified for the AP Scholar Award by completing three or more AP exams, with scores of 3 or higher. The AP Scholars are Chelsea Arndt, Mary Beckman, Elizabeth Drenzek, Alexis Drifka, Kathryn Erickson, Jeffrey Glisch, Jacob Goebl, Benjamin Hlavacek, Andrew Holten, Kristen Kaiser, Bryan Kubel, Alyssa Leidel, Jayme Lepak, Anne Li, Zachary Matusinec, Bradley Mayer, Kayla Muza, Andrea Pileggi, Allan Prichard, Emily Rapp, Kaitlyn Rinka, Angela Schulist, Natalie Sobierajski, Kelly Spoerk, Haley Steiner, Samantha Stovich, Cody Swendrowski, Amy Upthagrove, Nathan Weis and Jennifer Wolf.
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- Muskego-Norway School Board includes police dogs to help search student property
- High ACTs achieved in local schools; New Berlin and Muskego High School students attain notable scor
- Senior taxi ridership drops as elderly users pass away; program in search of new passengers
- New Berlin and Muskego police reports: August 14, 2014 issue
- Charity event to feature fashion in Muskego
- Musekgo High School employs sex offender security system
- Upcoming annual Muskego Community Festival will be a highflying event.
- Muskego Plan Commission shuns changes for lake homes, senior condos
- Retired Muskego High School principal will serve as interim replacement for Ryan Oertel


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Publications (55)136.82 Total impact
Article: Serum metabolic profiling study of lung cancer using ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: Lung cancer is currently the leading cause of cancer-related mortality worldwide. It is, therefore, important to enhance understanding and add a new auxiliary detection tool of lung cancer. In this work, serum metabolic characteristics of lung cancer were investigated with a non-targeted metabolomics method. The metabolic profiling of 23 patients with lung cancer and 23 healthy controls were analyzed using ultra high performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Partial least squares discriminant analysis (PLS-DA) model of the metabolic data allowed the clear separation of the lung cancer patients from the healthy controls. In total, 27 differential metabolites were identified, which were mostly related to the perturbation of lipid metabolism, including choline, free fatty acids, lysophosphatidylcholines, etc. Choline and linoleic acid were defined as one combinational biomarker using binary logistic regression, which was supported by the validation with a smaller sample-set (9 patients and 9 healthy controls). These findings show that LC/MS-based serum metabolic profiling has potential application in complementary identification of lung cancer patients, and could be a powerful tool for cancer research.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 05/2014; · 2.78 Impact Factor
Article: Serum Metabolomics Study of the Acute Graft Rejection in Human Renal Transplantation Based on Liquid Chromatography-Mass Spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: Acute graft rejection is one of the most common and serious post complications in renal transplantation. Non-invasive method is needed to specifically monitor acute graft rejection. We investigated metabolic alterations of acute graft rejection in human renal transplantation by applying a metabolomics approach. Sera from 11 acute graft rejection subjects and 16 non-acute graft rejection subjects were analyzed by a non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach including both hydrophilic interaction chromatography and reversed-phase liquid chromatography separations. Discriminative metabolites of acute graft rejection after transplantation were detected including creatinine, kynurenine, uric acid, poly-unsaturated fatty acid, phosphatidylcholines, sphingomyelins, lysophosphatidylcholines, etc. The lower level of serum dehydroepiandrosterone sulfate was found in acute graft rejection group before transplantation. The results revealed comprehensive metabolic abnormalities in acute graft rejection. The findings are valuable for the clinic noninvasive diagnosis or therapy of acute graft rejection.Journal of Proteome Research 03/2014; · 5.06 Impact Factor
Article: Serum metabolomics study of polycystic ovary syndrome based on liquid chromatography-mass spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: Polycystic ovary syndrome (PCOS) is a complex, heterogeneous disorder, which produces in 5%-10% reproductive age women. In this study, a non-targeted metabolomics approach based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry is used to investigate serum metabolic characteristics of PCOS. PCOS women and healthy control can be clustered into two distinct groups based on multivariate statistical analysis. Significant increase in the levels of unsaturated free fatty acids, fatty acid amides, sulfated steroids, glycated amino acid and the decrease in levels of lysophosphatidylcholines, lysophosphatidylethanolamines etc. were found. These metabolites showed abnormalities of lipid- and androgen-metabolism, increase of stearoyl -CoA desaturase (SCD) activity and accumulation of advanced glycation end-products in PCOS patients. Based on the binary logistic regression model, free fatty acid (FFA) 18:1/FFA 18:0, FFA 20:3, dihydrotestosterone sulfate, glycated phenylalanine and uridine were combined as a diagnostic biomarker. The area under the curve (AUC) of combinational biomarker was 0.839 in 131 discovery phase samples, and 0.874 in 109 validation phase samples. The findings of our study offer a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may provide a prospect for PCOS diagnosis.Journal of Proteome Research 01/2014; · 5.06 Impact Factor
Article: Serum metabolic profiling study of lung cancer using ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry[Show abstract] [Hide abstract]
ABSTRACT: Lung cancer is currently the leading cause of cancer-related mortality worldwide. It is, therefore, important to enhance understanding and add a new auxiliary detection tool of lung cancer. In this work, serum metabolic characteristics of lung cancer were investigated with a non-targeted metabolomics method. The metabolic profiling of 23 patients with lung cancer and 23 healthy controls were analyzed using ultra high performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS). Partial least squares discriminant analysis (PLS-DA) model of the metabolic data allowed the clear separation of the lung cancer patients from the healthy controls. In total, 27 differential metabolites were identified, which were mostly related to the perturbation of lipid metabolism, including choline, free fatty acids, and lysophosphatidylcholines etc. Choline and linoleic acid were defined as one combinational biomarker using binary logistic regression, which was supported by the validation with a smaller sample-set (9 patients and 9 healthy controls). These findings show that LC/MS-based serum metabolic profiling has potential application in complementary identification of lung cancer patients, and could be a powerful tool for cancer researchJournal of Chromatography B. 01/2014;
Article: Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: Method development and application in hepatocellular carcinoma.[Show abstract] [Hide abstract]
ABSTRACT: Sphingolipids are a family of bioactive molecules with high structural diversity and complexity. They not only serve as integral components of cellular membrane, but also play pivotal roles in signaling and other cellular events. It is desirable for the development of sensitive, robust and structural-specific analytical approaches enabling rapid determination of as many sphingolipid species as possible. Herein we present an analytical method for large-scaled profiling of sphigolipids in human serum, which consisted of an improved extraction protocol using tert-butyl methyl ether combined with mild alkaline hydrolysis, and an ultra high performance reversed-phase liquid chromatography-dynamic multiple reaction monitoring-mass spectrometric (RPLC-dynamic MRM-MS) method. In total 84 endogenous sphingolipid species covering six subcategories (i.e. free sphingoid base, dihydroceramide, ceramide, hexosylceramide, lactosylceramide, and sphingomyelin), were separated and quantified in a single run within 10min. A broad linear range over 2.5-4 orders of magnitude (r(2)>0.99), a limit of detection of 0.01-0.17pmol/mL, and a limit of quantitation of 0.02-0.42pmol/mL were obtained for each subcategory. Average recovery of each subcategory was within 85.6-95.6%. Median values of coefficient of variation (CV) of all detected 84 sphingolipids were 3.9% and 6.8% for intraday and interday precision, respectively. This method was exemplarily applied in a study regarding dysregulated sphingolipid homeostasis in hepatocellular carcinoma. The establishment of this method provides a useful tool for serum-based high throughput screening of sphingolipid biomarkers and mechanism investigation of sphingolipid metabolic regulation in human disease.Journal of Chromatography A 10/2013; · 4.61 Impact Factor
Article: Serum lipid profiling of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma by ultra fast LC/IT-TOF MS.[Show abstract] [Hide abstract]
ABSTRACT: In this study, an ultra fast LC/IT-TOF MS (UFLC/IT-TOF MS)-based serum lipidomics method was employed to characterize the serum lipid profile of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). After data collection and processing, 96 lipids including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, triacylglycerides, and cholesterol esters were identified and used for subsequent data analysis. Partial least squares-discriminant analysis revealed that patients with liver diseases had distinctly different serum lipid profile from that of healthy controls; while cirrhosis and HCC patients had a similar serum lipid profile, but different from that of hepatitis patients. The ANOVA analysis found 75 of the 96 identified lipids to be abnormally regulated, among which most of these lipids were downregulated in cirrhosis and HCC patients compared with those of healthy controls and hepatitis patients, while hepatitis patients induced several lipids downregulated and others upregulated compared with those of healthy controls, indicating the aberrant lipid metabolism in patients with liver diseases. This work demonstrated the utility of UFLC/IT-TOF MS-based serum lipidomics as a powerful tool to investigate the lipid metabolism of liver diseases.Electrophoresis 10/2013; 34(19):2848-56. · 3.26 Impact Factor
Article: Simultaneous extraction of metabolome and lipidome with methyl tert-butyl ether from a single small tissue sample for ultra-high performance liquid chromatography/mass spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: A common challenge for scientists working with animal tissue or human biopsy samples is the limitation of material and consequently, the difficulty to perform comprehensive metabolic profiling within one experiment. Here, we present a novel approach to simultaneously perform targeted and non-targeted metabolomics as well as lipidomics from one small piece of liver or muscle tissue by ultra-high performance liquid chromatography/mass spectrometry (UHPLC/MS) following a methyl tert-butyl ether (MTBE)-based extraction. Equal relative amounts of the resulting polar and non-polar fractions were pooled, evaporated and reconstituted in the appropriate solvent for UHPLC/MS analysis. This mix was comparable or superior in yield and reproducibility to a standard 80% methanol extraction for the profiling of polar and lipophilic metabolites (free carnitine, acylcarnitines and FFA). The mix was also suitable for non-targeted metabolomics, an easy measure to increase the metabolite coverage by 30% relative to using the polar fraction alone. Lipidomics was performed from an aliquot of the non-polar fraction. This novel strategy could successfully be applied to one mouse soleus muscle with a dry weight of merely 2.5mg. By enabling a simultaneous profiling of lipids and metabolites with mixed polarity while saving material for molecular, biochemical or histological analyses, our approach may open up new perspectives toward a comprehensive investigation of small, valuable tissue samples.Journal of Chromatography A 05/2013; · 4.61 Impact Factor
Article: Production and Release of Acylcarnitines by Primary Myotubes Reflect the Differences in Fasting Fat Oxidation of the Donors.[Show abstract] [Hide abstract]
ABSTRACT: Context:Acylcarnitines are biomarkers of incomplete β-oxidation and mitochondrial lipid overload but indicate also high rates of mitochondrial fatty acid oxidation. It is unknown whether the production of acylcarnitines in primary human myotubes obtained from lean, metabolically healthy subjects reflects the fat oxidation in vivo.Objective:Our objective was to quantify the acylcarnitine production in myotubes obtained from subjects with low and high fasting respiratory quotient (RQ).Methods:Fasting RQ was determined by indirect calorimetry. Muscle biopsies from the vastus lateralis muscle were taken from 6 subjects with low fasting RQ (mean 0.79 ± 0.03) and 6 with high fasting RQ (0.90 ± 0.03), and satellite cells were isolated, cultured, and differentiated to myotubes. Myotubes were cultivated with 125μM (13)C-labeled palmitate for 30 minutes and 4 and 24 hours. Quantitative profiling of 42 intracellular and 31 extracellular acylcarnitines was performed by stable isotope dilution-based metabolomics analysis by liquid chromatography coupled to mass spectrometry.Results:Myotubes from donors with high fasting RQ produced and released significant higher amounts of medium-chain acylcarnitines. High (13)C8 and (13)C10 acylcarnitine levels in the extracellular compartment correlated with high fasting RQ. The decreased expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD) in these myotubes can explain the higher rate of incomplete fatty acid oxidation. A lower intracellular [(13)C]acetylcarnitine to carnitine and lower intracellular (13)C16/(13)C18 acylcarnitine to carnitine ratio indicate reduced fatty acid oxidation capacity in these myotubes. Mitochondrial DNA content was not different.Conclusion:Acylcarnitine production and release from primary human myotubes of donors with high fasting RQ indicate a reduced fatty acid oxidation capacity and a higher rate of incomplete fatty acid oxidation. Thus, quantitative profiling of acylcarnitine production in human myotubes can be a suitable tool to identify muscular determinants of fat oxidation in vivo.The Journal of clinical endocrinology and metabolism 04/2013; · 6.50 Impact Factor
Article: Stable isotope-assisted lipidomics combined with non-targeted isotopomer filtering, a novel tool to unravel the complex dynamics of lipid metabolism.[Show abstract] [Hide abstract]
ABSTRACT: Investigations of complex metabolic mechanisms and networks have become a focus of research in the post-genomic area, thereby creating an increasing demand for sophisticated analytical approaches. One such tool are lipidomics analyses that provide a detailed picture of the lipid composition of a system at a given time. Introducing stable isotopes into the studied system can additionally provide information on the synthesis, transformation and degradation of individual lipid species. Capturing the entire dynamics of lipid networks, however, is still a challenge. We developed and evaluated a novel strategy for the in-depth analysis of the dynamics of lipid metabolism with the capacity for high molecular specificity and network coverage. The general workflow consists of stable isotope-labeling experiments, ultra high-performance liquid chromatography (UHPLC)-high resolution Orbitrap-MS lipid profiling and data processing by a software tool for global isotopomer filtering and matching. As a proof of concept, this approach was applied to the network-wide mapping of dynamic lipid metabolism in primary human skeletal muscle cells cultured for 4, 12 and 24 h with [U-13C]-palmitate. In the myocellular lipid extracts 692 isotopomers were detected that could be assigned to 203 labeled lipid species spanning 12 lipid (sub-) classes. Interestingly, some lipid classes showed high turnover rates but stable total amounts while the amount of others increased in the course of palmitate treatment. The novel strategy presented here has the potential to open new detailed insights into the dynamics of lipid metabolism that may lead to a better understanding of physiological mechanisms and metabolic perturbations.Analytical Chemistry 03/2013; · 5.70 Impact Factor
Article: Preanalytical Aspects and Sample Quality Assessment in Metabolomics Studies of Human Blood.[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Metabolomics is a powerful tool that is increasingly used in clinical research. Although excellent sample quality is essential, it can easily be compromised by undetected preanalytical errors. We set out to identify critical preanalytical steps and biomarkers that reflect preanalytical inaccuracies.METHODS: We systematically investigated the effects of preanalytical variables (blood collection tubes, hemolysis, temperature and time before further processing, and number of freeze-thaw cycles) on metabolomics studies of clinical blood and plasma samples using a nontargeted LC-MS approach.RESULTS: Serum and heparinate blood collection tubes led to chemical noise in the mass spectra. Distinct, significant changes of 64 features in the EDTA-plasma metabolome were detected when blood was exposed to room temperature for 2, 4, 8, and 24 h. The resulting pattern was characterized by increases in hypoxanthine and sphingosine 1-phosphate (800% and 380%, respectively, at 2 h). In contrast, the plasma metabolome was stable for up to 4 h when EDTA blood samples were immediately placed in iced water. Hemolysis also caused numerous changes in the metabolic profile. Unexpectedly, up to 4 freeze-thaw cycles only slightly changed the EDTA-plasma metabolome, but increased the individual variability.CONCLUSIONS: Nontargeted metabolomics investigations led to the following recommendations for the preanalytical phase: test the blood collection tubes, avoid hemolysis, place whole blood immediately in ice water, use EDTA plasma, and preferably use nonrefrozen biobank samples. To exclude outliers due to preanalytical errors, inspect the biomarker signal intensities reflecting systematic as well as accidental and preanalytical inaccuracies before processing the bioinformatics data.Clinical Chemistry 02/2013; · 7.15 Impact Factor
Article: Independent component analysis in non-hypothesis driven metabolomics: Improvement of pattern discovery and simplification of biological data interpretation demonstrated with plasma samples of exercising humans.[Show abstract] [Hide abstract]
ABSTRACT: In a non-hypothesis driven metabolomics approach plasma samples collected at six different time points (before, during and after an exercise bout) were analyzed by gas chromatography-time of flight mass spectrometry (GC-TOF MS). Since independent component analysis (ICA) does not need a priori information on the investigated process and moreover can separate statistically independent source signals with non-Gaussian distribution, we aimed to elucidate the analytical power of ICA for the metabolic pattern analysis and the identification of key metabolites in this exercise study. A novel approach based on descriptive statistics was established to optimize ICA model. In the GC-TOF MS data set the number of principal components after whitening and the number of independent components of ICA were optimized and systematically selected by descriptive statistics. The elucidated dominating independent components were involved in fuel metabolism, representing one of the most affected metabolic changes occurring in exercising humans. Conclusive time dependent physiological changes of the metabolic pattern under exercise conditions were detected. We conclude that after optimization ICA can successfully elucidate key metabolite pattern as well as characteristic metabolites in metabolic processes thereby simplifying the explanation of complex biological processes. Moreover, ICA is capable to study time series in complex experiments with multi-levels and multi-factors.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2012; · 2.78 Impact Factor
Article: Metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: Acute graft rejection is one of the most common and serious post complications in renal transplantation, noninvasive diagnosis of acute graft rejection is essential for reducing risk of surgery and timely treatment. In this study, a non-targeted metabonomics approach based on ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (MS) is used to investigate the effect of acute graft rejection in rat renal transplantation on metabolism. To collect more metabolite information both hydrophilic interaction chromatography and reversed-phase liquid chromatography were used. Using the partial least squares-discriminant analysis, we found that the change of metabonome in a sham-operated group and a non-graft rejection group had a similar trend, while that of the acute graft rejection group was clearly different. Several discriminating metabolites of the acute graft rejection were identified, including creatinine, phosphatidyl-cholines, lyso-phosphatidylcholines, carnitine C16:0, free fatty acids and indoxyl sulfate etc. These discriminating metabolites suggested that acute graft rejection in renal transplantation can lead to the accumulation of creatinine in the body, and also the abnormal metabolism of phospholipids. These findings are useful to understand the mechanisms of the rejection, it also means that a UPLC-MS metabonomic approach is a suitable tool to investigate the metabolic abnormality in the acute graft rejection in renal transplantation.Molecular BioSystems 03/2012; 8(3):871-8. · 3.35 Impact Factor
Article: Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis.[Show abstract] [Hide abstract]
ABSTRACT: The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target metabolomics method, and test their usefulness in early human HCC diagnosis. The serum metabolic profiling of the diethylnitrosamine-induced rat HCC model, which presents a stepwise histopathological progression that is similar to human HCC, was performed using liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Three metabolites, taurocholic acid, lysophosphoethanolamine 16:0, and lysophosphatidylcholine 22:5, were defined as "marker metabolites," which can be used to distinguish the different stages of chemical hepatocarcinogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients. To test their diagnosis potential 412 sera from 262 patients with HCC, 76 patients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumor (solitary nodules of less than 2 cm in diameter) patients, achieved a sensitivity of 80.5% and a specificity of 80.1%,which is better than those of α-fetoprotein (53 and 64%, respectively). Moreover, they were also effective for the discrimination of all HCCs and chronic liver disease patients, which could achieve a sensitivity of 87.5% and a specificity of 72.3%, better than those of α-fetoprotein (61.2 and 64%). These results indicate metabolomics method has the potential of finding biomarkers for the early diagnosis of HCC.Molecular & Cellular Proteomics 11/2011; 11(2):M111.010694. · 7.25 Impact Factor
Conference Paper: Metabolic Biomarker Discovery and Confirmation by Using Metabonomics7th International Conference of the Metabolomics Society; 01/2011
Article: Urinary metabolic profiling of colorectal carcinoma based on online affinity solid phase extraction-high performance liquid chromatography and ultra performance liquid chromatography-mass spectrometry.[Show abstract] [Hide abstract]
ABSTRACT: Colorectal carcinoma (CRC) is the third most commonly encountered cancer and fourth cause of cancer-associated death worldwide. Abundant studies have demonstrated that one of the best effective therapies for enhancing the 5-year survival rate of patients is to diagnose the disease at an early stage. Urine metabonomics is widely being utilized as an efficient platform to investigate the metabolic changes and discover the potential biomarkers of malignant diseases. In this study both ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and online affinity solid phase extraction-high performance liquid chromatography (SPE-HPLC) were used to analyze the urinary metabolites from 34 healthy volunteers, 34 benign colorectal tumor and 50 colorectal carcinoma patients to produce comprehensive metabolic profiling data. A reliable separation between the control and disease groups as well as significantly changed metabolites were obtained from orthogonal signal correction partial least squares models which were built based on the two separate data sets from UPLC-MS and affinity SPE-HPLC, respectively. 15 metabolites, showing the metabolic disorders of CRC, were identified finally. These metabolites were found to be related to glutamine metabolism, fatty acid oxidation, nucleotide biosynthesis and protein metabolism.Molecular BioSystems 10/2010; 6(10):1947-55. · 3.35 Impact Factor
Article: Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits.[Show abstract] [Hide abstract]
ABSTRACT: Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for decades is associated with multiple metabolic alterations in insulin sensitive tissues. In an UPLC-qTOF-mass spectrometry-driven non-targeted metabonomics approach we investigated plasma as well as spot urine of 51 non-diabetic, overnight fasted individuals aiming to separate subjects with IGT from controls thereby identify pathways affected by the pre-diabetic metabolic state. We could clearly demonstrate that normal glucose tolerant (NGT) and IGT subjects clustered in two distinct groups independent of the investigated metabonome. These findings reflect considerable differences in individual metabolite fingerprints, both in plasma and urine. Pre-diabetes associated alterations in fatty acid-, tryptophan-, uric acid-, bile acid-, and lysophosphatidylcholine-metabolism, as well as the TCA cycle were identified. Of note, individuals with IGT also showed decreased levels of gut flora-associated metabolites namely hippuric acid, methylxanthine, methyluric acid, and 3-hydroxyhippuric acid. The findings of our non-targeted UPLC-qTOF-MS metabonomics analysis in plasma and spot urine of individuals with IGT vs NGT offers novel insights into the metabolic alterations occurring in the long, asymptomatic period preceding the manifestation of T2DM thereby giving prospects for new intervention targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0203-1) contains supplementary material, which is available to authorized users.Metabolomics 09/2010; 6(3):362-374. · 4.43 Impact Factor
Conference Paper: Comprehensive Identification of Metabolic Biomarkers in HPLC MS Based Metabonomics58th Annual Conference on Mass Spectrometry,Japan & 1st Asian and Oceanic Mass Spectrometry Conference; 01/2010
Article: Insulin sensitivity is reflected by characteristic metabolic fingerprints--a Fourier transform mass spectrometric non-targeted metabolomics approach.[Show abstract] [Hide abstract]
ABSTRACT: A decline in body insulin sensitivity in apparently healthy individuals indicates a high risk to develop type 2 diabetes. Investigating the metabolic fingerprints of individuals with different whole body insulin sensitivity according to the formula of Matsuda, et al. (ISI(Matsuda)) by a non-targeted metabolomics approach we aimed a) to figure out an unsuspicious and altered metabolic pattern, b) to estimate a threshold related to these changes based on the ISI, and c) to identify the metabolic pathways responsible for the discrimination of the two patterns. By applying infusion ion cyclotron resonance Fourier transform mass spectrometry, we analyzed plasma of 46 non-diabetic subjects exhibiting high to low insulin sensitivities. The orthogonal partial least square model revealed a cluster of 28 individuals with alterations in their metabolic fingerprints associated with a decline in insulin sensitivity. This group could be separated from 18 subjects with an unsuspicious metabolite pattern. The orthogonal signal correction score scatter plot suggests a threshold of an ISI(Matsuda) of 15 for the discrimination of these two groups. Of note, a potential subgroup represented by eight individuals (ISI(Matsuda) value between 8.5 and 15) was identified in different models. This subgroup may indicate a metabolic transition state, since it is already located within the cluster of individuals with declined insulin sensitivity but the metabolic fingerprints still show some similarities with unaffected individuals (ISI >15). Moreover, the highest number of metabolite intensity differences between unsuspicious and altered metabolic fingerprints was detected in lipid metabolic pathways (arachidonic acid metabolism, metabolism of essential fatty acids and biosynthesis of unsaturated fatty acids), steroid hormone biosyntheses and bile acid metabolism, based on data evaluation using the metabolic annotation interface MassTRIX. Our results suggest that altered metabolite patterns that reflect changes in insulin sensitivity respectively the ISI(Matsuda) are dominated by lipid-related pathways. Furthermore, a metabolic transition state reflected by heterogeneous metabolite fingerprints may precede severe alterations of metabolism. Our findings offer future prospects for novel insights in the pathogenesis of the pre-diabetic phase.PLoS ONE 01/2010; 5(10):e13317. · 3.73 Impact Factor
Conference Paper: Metabolic Biomarker Discovery of Complicated Diseases by Using LC-MS Based Metabonomics5th Shanghai International Symposium on Analytical Chemistry; 01/2010
Article: Medium chain acylcarnitines dominate the metabolite pattern in humans under moderate intensity exercise and support lipid oxidation.[Show abstract] [Hide abstract]
ABSTRACT: Exercise is an extreme physiological challenge for skeletal muscle energy metabolism and has notable health benefits. We aimed to identify and characterize metabolites, which are components of the regulatory network mediating the beneficial metabolic adaptation to exercise. First, we investigated plasma from healthy human subjects who completed two independent running studies under moderate, predominantly aerobic conditions. Samples obtained prior to and immediately after running and then 3 and 24 h into the recovery phase were analyzed by a non-targeted (NT-) metabolomics approach applying liquid chromatography-qTOF-mass spectrometry. Under these conditions medium and long chain acylcarnitines were found to be the most discriminant plasma biomarkers of moderately intense exercise. Immediately after a 60 min (at 93% V(IAT)) or a 120 min run (at 70% V(IAT)) a pronounced, transient increase dominated by octanoyl-, decanoyl-, and dodecanoyl-carnitine was observed. The release of acylcarnitines as intermediates of partial beta-oxidation was verified in skeletal muscle cell culture experiments by probing (13)C-palmitate metabolism. Further investigations in primary human myotubes and mouse muscle tissue revealed that octanoyl-, decanoyl-, and dodecanoyl-carnitine were able to support the oxidation of palmitate, proving more effective than L-carnitine. Medium chain acylcarnitines were identified and characterized by a functional metabolomics approach as the dominating biomarkers during a moderately intense exercise bout possessing the power to support fat oxidation. This physiological production and efflux of acylcarnitines might exert beneficial biological functions in muscle tissue.PLoS ONE 01/2010; 5(7):e11519. · 3.73 Impact Factor
Top Journals
Dalian Institute of Chemical PhysicsLü-ta-shih, Liaoning, China
Xinjiang Medical UniversityOuroumtchi, Xinjiang Uygur Zizhiqu, China
Northeast Institute of Geography and Agroecology
Beijing, Beijing Shi, China
- Laboratory of Analytical Chemistry for Life Science
Second Military Medical University, Shanghai
Shanghai, Shanghai Shi, China
- International Cooperation Laboratory on Signal Transduction
Helmholtz-Zentrum für Umweltforschung
Leipzig, Saxony, Germany
- Department Ökologische Chemie
Chinese Academy of SciencesPeping, Beijing, China


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Hamburgers themselves can be served in many different ways. The most common way to serve a hamburger is to put the patty between two halves of a hamburger roll but you can also serve hamburgers in gravy or in sauce.
Healthy Side Dishes
If you want to balance an indulgent hamburger recipe or cheeseburger recipe with something nutritious, there are plenty of options. If you are wondering what to serve with hamburgers on a hot day, what about a crisp, fresh salad?
You can use whatever salad ingredients you have in the refrigerator to make a tasty salad. Lettuce, onion, tomato, beets, chopped boiled egg, and nuts make a nice salad and you can either serve salad dressing on the side or drizzle some over the salad just before serving. Do not put it on too early, else the salad will go limp and soggy.
Vegetables make good side dishes too, if you are thinking about what to serve with hamburgers. If you are grilling your hamburgers you can also make some grilled vegetable recipes as an accompaniment. Corn on the cob, bell peppers, mushrooms and onion all grill beautifully and easy grilled vegetable kabobs look great and taste amazing.
You might like to serve a baked potato with your hamburger recipes and you can partially cook it in the microwave and finish it off on the grill if you want to.
Not So Healthy Side Dishes
Sometimes the not so healthy hamburger side dishes are the most enjoyable and traditional hamburger side dishes include French fries, onion rings, fried potato wedges and more.
What to serve with hamburgers also depends on the size of the hamburgers. If you are simply serving hamburger patties or sloppy joes, you can make mashed potatoes, boiled vegetables, and gravy. If you are making double bacon cheeseburgers, that might be a meal in itself and require no side dishes!
If you are having a cookout, what about preparing a few side dishes that people can help themselves to? Some of your guests might want some salad, French fries, onion rings or whatever and others might be happy with just their hamburgers.
A Selection of Hamburger Toppings
Macaroni salad, baked beans and pasta salad are all nice with hamburgers and you can also serve hamburger toppings for people to help themselves to.
Hamburger toppings, which people can add at the end of the hamburger cooking time, include cheese slices, lettuce, tomato, pickles, and beets. You can leave these out so people can select their preferred toppings when the hamburgers are done.
If you are going to make fried eggs as hamburger toppings you will want to find out in advance how many people want them because they do not do very well sitting around in the sun! The same applies to cheese and you should find out in advance who wants hamburgers and who would prefer cheeseburgers. The cheese should melt over the hamburger patty, not on the table waiting for the hamburger to finish cooking!
What to serve with hamburgers varies from person to person. Some people adore the flavor of beef and want nothing more than the flavor of the beef and the flavor of the hamburger bun it is served in. It is a good idea to prepare a few side dishes though. If you are in a rush, keep it simple with French fries and salad or corn on the cob and potato salad and everyone will be happy.
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Ann Charlene (Pemberton) Liptrap
PERU — Ann Charlene (Pemberton) Liptrap, 82, Peru, passed away at 1:20 p.m. Saturday, May 3, 2014, at Miller's Merry Manor Nursing Home, Peru.
She was born Nov. 16, 1931, at Pendleton, to Odin and Gertrude (Sanders) Pemberton. She married Clarence Liptrap on July 2, 1949, in Morganfield, Ky. He passed away July 14, 2004, after 55 years of marriage.
Ann had been retired since 1997 after 47 years from olin corps and standard Fusee.
She is survived by one child, S. Lee Liptrap, and close friend, Margie Stout, Peru.
She was preceded in death by both parents; husband, Clarence Liptrap; sister, Wanda Lucille Pemberton; and brother, Robert Samuel Pemberton.
A graveside service will be at 11 a.m. Monday in the Bethel Memorial Cementery, Mount Vernon, Ill.
Friends may call from 10 a.m. to noon Friday at Flowers-Leedy Funeral Home, Peru. Then she will be taken to Hughey Funeral Home in Mount Vernon, Ill. Friends may also call from 10 a.m. until the time of the graveside service Monday at the cemetery.
The family would also like to thank all the nurses and staff at Millers Merry Manor Nursing Home for taking real good care of her.
Arrangements have been entrusted to Flowers-Leedy Funeral Home.


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Boyertown SC hosts the 2nd Annual Boyertown Blast on Saturday 11/22/14 for girls age groups U9-U12 (8v8) and U13 (11v11). There is a 3 game guarantee. Cost: U9-U12 - $400, U13 - $450. Register by 9/13/14 and save $25 off the registration fee. For more information contact the Tournament Director Lenny Toscano. To register click HERE.
LDC United will host the LDC United Coppa Classico on 10/11-12/2014. The tournament is for all levels of play, age groups U9 to U15 for boys and girls. A 11v11 bracket is being offered for U12 boys and U12 girls in addition to the 8v8 format. Three field sites using Quality grass and turf fields. For more information and to register click HERE.
Whether you are a State Champ or a New Team just beginning the travel soccer experience, Penn Legacy offers appropriate and challenging levels of competition for your team. TJoin the 575 teams and 8000 players that will celebrate our 29th year with a run at a championship trophy to top off their Fall season. Visit Penn Legacy for more info.
US Youth Soccertoday has announced Axon Sports as a long-term strategic partner for computerized baseline testing for concussion management, leading the way in making soccer safer for kids at the grassroots level. Through the relationship, US Youth Soccer will provide member discounts and educational resources on USYouthSoccer.org. It will also provide more than 25,000 US Youth Soccer players free access to the Axon Sports Computerized Cognitive Assessment Tool (CCAT).
Thomas Jefferson University Hospital, Rothman Institute and Wills Eye Hospital have collaborated to establish the Jefferson Comprehensive Concussion Center (J.C.C.C.) at the Philadelphia Navy Yard. The J.C.C.C. will be among the very few concussion centers in the nation to provide clinical care in areas such as neuro-opthalmology, neuroradiology, psychiatry, and complex rehabilitation at one facility.
If you are a player looking for a team or a team looking to add a player(s), PAGS has a Player/Team Bulletin Board to help players and teams find each other. Teams looking for players should complete the attached form and submit it to PAGS. This form will be posted to the PAGS Bulletin Board. Interested players can contact the team via email. Please check the Bulletin Board under Tryout Announcements under related links on the left-hand side of the home page for further information. Click HERE to access the team information form for the PAGS Player/Team Bulletin Board.
PAGS is soliciting donations of gently used equipment and uniforms for our Outreach Program. We will accept uniforms, balls, ball bags, cones/discs, shin gurads, shoes, and any other soccer related other equipment. These items will be forwarded to Clubs in inner-city Philadelphia, te Carribean, and South America as part of the League outreach to disadvantaged soccer players. To make donations contact PAGS at firstname.lastname@example.com.
PAGS introduces a new feature to benefit Delegates, coaches, players and parents called Frequently Asked Questions or FAQs. Just go to the FAQ link on the right-hand side on the home page under 'PAGS Headlines'. There you will find FAQs for general information, Delegate information, information for Coaches, and Registration information.
Please check the FAQ pages before you email the League for an answer.
The preliminary 2014 fall season schedule will be released to the Clubs on 7/3/14. In order to schedule your home games you will need to have all the fields you will be utilizing this fall entered into the PAGS database. In addition, you will need to enter permit information for each field in order for the Referee Assignor to be notified of game changes once the final schedule is released. If you have utilized a field in a previous season it will be in the database, but you will still need to update the permit information to include the 2014 fall season.
Instructions for entering field and permit information may be found HERE.
For the Fall 2014 season PAGS will utilize the scheduling system used during the Spring 2013 and Fall 2013 seasons. Any person with administrative rights to the PAGS website for each club will be able to directly enter the time and field for all the club home games on the PAGS website.
Registration materials (player/coach pass stock) were handed out to all Pennsylvania clubs that attended the joint Delco SL/PAGS registrar meeting held on Tuesday, 6/24/14. Clubs that failed to attend the meeting can pick up card stock for their PAGS teams at the PAGS office building between 8:00 am and 5:00 pm, Monday through Friday, beginning Friday, 6/27/14. There will be envelopes for each club in a container inside the lobby of the building. The PAGS office is located at 458 E. King Rd., Malvern, PA 19355. Due to costs involved PAGS will NOT mail card stock. If you cannot pick up envelope you may contact EPYSA to obtain card stock.
The key dates for PAGS for 2014 can be found on the next page.
Fees for the 2014-2015 seasonal year are available below.
The PAGS fine schedule for the 2013-2014 seasonal year is available below.
Building on the success of the 2013 Fall season, PAGS will again offer strictly developmental play U9 and U10 for the 2014 Fall season. At U11 to U14 we will offer competitive and developmental levels, while U15-U19 will be competitive only. We will again do this by offering two separate conferences within PAGS. The competitive conference will be known as the PAGS Premier Conference and the developmental conference will be known as the PAGS Charlotte Moran Conference.
Small-Sided Age Groups
U9-U10 - Developmental (8v8)
U11-U12 - Competitive (8v8) and Developmental (8v8)
Full-Sided Age Groups
U13-U14 - Competitive (11v11) and Developmental (11v11)
U15-U19 - Competitive (11v11) Long season and short season
The PAGS Appeals Committee considered all appeals to the preliminary divisional placements for the PAGS 2014 Fall season. The Committee granted 45 appeals while denying 13. No further appeals of divisional placements will be considered.
Teams have until 6:00 pm on Wednesday, 6/18/14, to withdraw from the PAGS fall season without financial penalty. Any team withdrawing after this time will forfeit its application fee.
The final divisional placements for the PAGS 2014 Fall season are available HERE .
PAGS will continue to utilize the scheduling system that began with the Spring 2013 season. PAGS will not be scheduling together with Delco SL. PAGS will generate the schedule with game number, date, and home/away teams. The person(s) with administrative rights to the PAGS website for each club will be able to directly enter on the PAGS website the time and field information for all club home games.


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