text:
Robin Augello
Village Party
Baldwinsville resident since 1991
Political experience:
Planning board for four months
Architectural review board for six months
Community involvement:
Baker High School musicals, Baldwinsville Little League, serve on the advisory board of Women TIES, a CNY based organization that promotes women business owners and entrepreneurs
How do you envision Baldwinsville's future?
I see a thriving river front community where people can come and live affordably while enjoying a wide range of nearby services. I see more and more visitors coming to Baldwinsville eating in our restaurants, staying a night or two, enjoying unique shopping while taking in the fabulous view.
Increasing property taxes and the current effort to consolidate seem to be two issues at the forefront. What is your take on these issues?
What is important for residents to understand is that our rising property taxes are, for the most part, a direct result of our increasing property values, which is a good thing. Whether you plan on selling your house or using your home's equity for any number of reasons, a higher value is always favorable. What we need to focus on is how money collected is spent and make sure we all know what we are getting in return. I am very much in favor of the study to determine how we can run a more cost-effective village. I love the sense of community that surrounds us and don't want to lose that, but at the same time we owe it to ourselves to investigate any possible alternatives as to how things are currently done. The fact that our current leaders, in the village and both towns, have agreed to this is excellent progress already.
In your opinion, what other issues are facing Baldwinsville? How do you intend to tackle these issues?
I see the vacant buildings that dot our landscape as current issues. Some of these buildings, such as the DPW on Lock Street or the old town hall, sit on prime waterfront property that offers possible development opportunities at no cost to taxpayers. A potential green space in place of the old firehouse is a great move, but we need to be proactive, investigate possible options, determine what is financially feasible, and make timely decisions. I believe there is a great potential for tourism development as well. The carp tournament heading our way is certainly a start, but once again, we can't wait for these opportunities to come to us. We are part of a canal system known worldwide I would like to see us working with local, regional and state tourism agencies and develop a plan. I know once visitors, fishermen, etc. discover Baldwinsville, they will the spread word about our vibrant, welcoming community. I think it is important to communicate, either via the media, the village web site or maybe a newsletter, to all residents what is happening in a clear, consistent manner.
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The room had all the things needed for a stay and business. They had free Wi-Fi. Access to a nice...
See full review
The room had all the things needed for a stay and business. They had free Wi-Fi. Access to a nice...
I stayed in Portopia Hotel for 3 nights to attend a conference. I really enjoyed the stay in...
See full review
I stayed in Portopia Hotel for 3 nights to attend a conference. I really enjoyed the stay in...
Customers who viewed Portopia Hotel also booked these hotels.
Rates quoted in currencies other than the hotel's base currency are subject to the rate of the international exchange. Rate may change throughout stay. Rate may reflect average nightly rate. Extra charges may apply. Incidental charges, such as room service, are not included in the rate.
The amenities and/or facilities may not be located at the hotel, but within a reasonable distance, and additional charges may apply for use. All information has been provided by this hotel and not by Orbitz
Overall score
Reviewer score
Would recommend
Nice hotel in slightly off location
Well kept and nice hotel with large clean rooms with excellent bathrooms and comfy beds. The rooms had no Wifi, but free internet through LAN-cable (provided). Great view from higher floors. The breakfast buffet was good and the view over Kobe
downtown and mountains was great, but ridiculously expensive if you pay for it separately (2500 yen). There are several resturants in the hotel. They all seem very expensive, we didn't try any of them.
The location of the hotel is slightly off (unless you are attending a meeting at the Kobe International Conference Center), to get into Kobe city you need to take the automatic train "Portliner" (2 min walk from hotel, 240 yen one way) or the hotel shuttle bus (free, runs every 20 ins until 10 pm).
Very nice gym located in the hotel (1050 yen fee if you train mornings, more expensive after lunch).
One bad thing is that check in is at 3 pm.
I would highly recommend the restaurant "Sun" in Kobe city! Slightly difficult to find, but well worth it! They don't speak a lot of English and the menu is only in Japaneese, but they are very helpful and have set menus (and they understand what you are saying if you ask for one of those). I had incredibly tasty food both days, and the helpfulness of the staff and the very Japaneese setting (and other guests) made it a cultural experience too.
The restaurant is located on the 10th floor of the building across the street from Sannomia station (north of store Marui), the easiest way to find it is to look for the Kobe Tourist information office, don't enter the builing but instead go through the glass doors to the left (on the outside) and take the elevator up to 10th floor.
The address is: Sannomiya 1-10-1, Kobe Kotsu Center Building 10F
Here is a review: http://www.bento.com/kansai/rev/9037.html
Business stay, wonderful choice.
I stayed in Portopia Hotel for 3 nights to attend a conference. I really enjoyed the stay in Portopia hotel. This hotel is close Kobe port. There is not many shops outside the hotel, except an café and IKEA, but there are quite a few nice
restaurant options in the hotel itself. I can find nice food with a reasonable price in the hotel. In addition, the hotel has free shuttle bus to Sannomiya and Shin-Kobe every 20 minutes, which is very convenient for customers. I used the swimming pool as well, and I love it! Finally, I thought the room size in Japan is usually very small, but not Portopia. I love the room size and service. I really appreciate the services Portopia provided and would definitely go back to stay again.
Great hotel.
The room had all the things needed for a stay and business. They had free Wi-Fi. Access to a nice walking/running route in the morning was great! I had a room on the 24th floor with a view of the Bay. I guess I can't complain!
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This weekend, we'll see sunny skies with highs in the mid to upper 60s. Lows will be in the mid 40s/upper 30s and winds will mostly come from the south around 5 to 15 mph.
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31 year old woman | Atlanta, GA, USA | Seeking men 29-35 within 50 miles
Enjoy life and continue re-discovering yourself!
I am a big believer of balance in life, which is what gets reflected in my choices in life as well as my personality. I love being out with friends and then take some time off to be alone. I love being outdoors doing activities like hiking, camping etc and then just laze around at home doing nothing. I enjoy luxury and yet have fun at the local dive bar. I love my job and also dream about running away to live a nomadic life. If you're still reading, then maybe we should talk! :)
Coffee and conversation , Dining out , Movies/Videos , Music and concerts , Exploring new areas , Performing arts , Playing sports , Travel/Sightseeing , Watching sports
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If I had one, it would probably be a Siberian Husky! Love them!
Middle of the Road
Bordeaux in France was the best city I ever visited. Some trips that I would love to do: Ladakh and backpacking across South Africa. Locally, I love the brunch at Old Highland Bakery, and to explore the cities culinary diversity...
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TV shows I watch: Bones, Burn Notice, Big Bang Theory, White Collar Movies: 300, Gladiator, The Dark Knight, Bourne Series, Lord of the Rings, etc (I'm a movie buff!)
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|5'11" (180cms) to 6'5" (195cms)
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3rd Party Cooler For GTX580?
View Single Post
Registered User
Join Date: May 2005
Posts: 17,982
Re: 3rd Party Cooler For GTX580?
Originally Posted by
Obviously that's not what i'm doing, I'm going by reviews and the GTX580 sitting inside my system plus information I've seen from other users who I trust.
70C load is BS unless your using a noisy custom fan profile.
Not necessarily. When the G80s first came out I picked up dual 640MB 8800GTSs. Everybody complained about how hot the 8800GTS and GTX ran, while both of mine never reached 60*C under full load I believe it was. Granted, the room I gamed in was cool and I had rediculous airflow in my case. None the less, it is possible even with the stock cooling and stock fan settings. Rare? Sure, but possible none the less.
I know the 8800s was some time back but that was just an example, the 8800s were hot running cards and to this day I'm not 100% sure how they ran so cool. But they did, neven even got too hot to touch even afte hours of rigorous gaming. If it happened with my 8800s, it could happen with his 580.
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Larry Hagman, oilman J.R. Ewing of 'Dallas,' dead at 81
J.R. Ewing was a business cheat, faithless husband and bottomless well of corruption. Yet with his sparkling grin, Larry Hagman masterfully created the charmingly loathsome oil baron and coaxed forth a Texas-size gusher of ratings on television's long-running and hugely successful nighttime soap, "Dallas." »Read Full Article(16)
Bad Religion; Jimmy Eat World; Trampled by Turtles; the Mavericks; VENA
Bad Religion
Rough estimate, by the critic's watch, of when Bad Religion began playing, hard, at the U.S. Cellular Connection Stage Sunday night: 10:01. Rough estimate of when the SoCal punk-rock band finished off its fourth song: 10:08. »Read Full Article(1)
Eagles take it easy at Marcus Amphitheater
The news flash from the Eagles' closing-night gig at Summerfest's Marcus Amphitheater on Sunday night is that Bernie Leadon appears to be at least partway back in the band.
Eagles' historians will remember that Leadon, an original band member, exited the group in rather definitive fashion way back in 1975 when he poured a bottle of beer over Glenn Frey's head. »Read Full Article(9)
Video: Tap Milwaukee music writers recap Summerfest 2013
Well, that's a wrap. Another Summerfest has come and gone.
What rocked, what didn't at Summerfest
After 11 days of concerts and crazy crowds, Summerfest becomes a bit of a blur. But there are a few clear takeaways from Summerfest 2013:
Favorite crowd observation: Watching a stern security guard, arms folded, grimace on his face, bobbing his head ever so subtly to New Kids on the Block. »Read Full Article(16)
Exclusive Video: Bachata supergroup VENA performs "Sangre De Mis Venas" at Summerfest
Last but certainly not least, Tap Milwaukee has one more exclusive video performance to share with you from Summerfest 2013, courtesy of bachata supergroup VENA.
On Tap Today: Summerfest rundown for July 7
Journal Sentinel music writer Piet Levy gives you the rundown on what to look forward to today at Summerfest. »Read Full Blog Post
Going for a swim? Check out guide to Milwaukee-area beaches, pools
It's warming up in a hurry this Sunday morning. Might be a good day for a swim — before storms roll in later today.
If you're in the mood for some waves, or just a trip to the beach, go to Tap Milwaukee's guide to area swimming spots, with hours and other info on southeast Wisconsin beaches and pools. »Read Full Article
Three to See: Suggestions for July 7
Something known: Eagles (7:30 p.m. Marcus Amphitheater). It's hardly a news flash to say the Eagles are a great band. But an extensive new documentary has brought a renewed sense of appreciation, transforming concerts from mere gigs to victorious events. »Read Full Article
Theatre open house; Runway sneak peak; Inspired art
Curtain up
In Tandem Theatre is giving patrons and future-patrons a chance to get a taste of its season for free Wednesday at the 7th Annual Sneak Peek & Open House. The troupe will perform tidbits from "Burying the Bones," "A Cudahy Caroler Christmas," and other plays while noshing on snacks and partaking at the cash bar. The peek takes place from 5:30 to 8:30 p.m. at its performing space, the Tenth Street Theatre, 628 N. 10th St. »Read Full Article


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text: Facebook [ American Cancer Society To Host 15th Annual Relay For Life This Weekend [AUDIO] By Ariel Walden May 8, 2013 On Wednesday's edition of Lubbock's First News, siblings Whitney, Barkley and Bryce White talked with Tom Collins and Laura Mac about the upcoming Relay For Life. Read More|Comment Category: Audio, Events, Lubbock News Tags: american cancer society, relay for life Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


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Unprofessional Fridays: Thursday Edition 07/02/2015
Become Premium to Watch
Her Story is a bold and largely successful experiment in interactive crime fiction.
Rocksteady's gorgeous-looking third Arkham game refines its open-world format a bit and lets you drive a whole hell of a lot of Batmobile.
It's squid kids and ink blasting abound in Nintendo's exceptionally fun new online shooter.
Location »
"AAAaaaAAAaaaAAAaaaAA—" BOOM!
Bison, also called Buffalo in America are large bovids with shaggy manes and short horns.
Bug Catcher is a Pokémon trainer that is always depicted holding a bug net. They often use weak bug Pokémon such as Caterpie and Kakuna, but also come in a variant called Bug Maniac in which they hold strong bug Pokémon like Heracross or Butterfree.
Dryads are tree nymphs from Greek mythology. They have made appearances in a number of games.
An elephant is the largest land mammal who has big ears, a trunk for a nose, a tail, and tusks. Supposedly they have good memories, hidden graveyards, a love of peanuts, and a great fear of mice.
Farming is the act of growing plants and raising animals for food.
An ancient economic system used in Medieval Europe and Japan.
Floating Islands are land masses (anywhere from island size to continental size) that float either by the use of magic or some other force.
Foxes are wolf-like mammals, many having red fur. They are thought of as tricksters, underdogs, or for women, if you're foxy, then you're sexy.
Halflings, also known as hobbits, average about three and a half feet tall. They have an innate affinity to nature and possess both the agility and dexterity to make great rogues. Halflings are generally good people, but also have a mischievous side that my infuriate others.
Equines that go 'neigh' and tend to eat hay. Some are the stars of motion pictures. The truest of companions to many adventurers.
Horse riding is mostly used in games to get around from one place to another quicker than you could on foot. They can also sometimes be used in combat or racing.
The hunter is a popular class archetype. The usually travel light and excell best at range combat with either guns or bows. Often pets are associated with hunters as they are known to tame wild beasts.
Enemies in RPGs that are visible on the overworld map and that are engaged in combat when touched. Examples include Earthbound and Paper Mario.
Jigglypuff is a normal type Pokémon that evolves from Igglybuff, and can into Wigglytuff with a Moon Stone. They love to sing.
Lions are currently the second largest felines walking planet Earth. They are often referred to as the king of the jungle.
Non-linear level design where the player is able to freely traverse the game world and choose where and when to visit certain areas in the game.
An overworld is a simplified view of the game world that allows players to freely move to different locations or levels.
Peasants are agricultural laborers and countryfolk who are working the land, usually for others. Hobbies include farming, paying taxes, getting in the way of swordfights and being eaten by dragons.
A graphical effect that shows a massive amount of world or is used to give a sense of grand scale.
A species of striped feline.
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Posted 11/17/2013 05:28:27 EST
You keep saying the 2004 Sox were the only team to win SI's Sportsmen of the year. You're wrong as the 1980 Olympic hockey team also received the honor. Get your facts straight. You may have to rewrit more »
Posted 03/31/2013 11:22:45 EDT
You said you would like to be owner for one season. I would love that so we can dump all over you. You're an idiot. more »
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Another Israeli company is headed for Nasdaq
Home Skinovations, which makes laser hair-removal equipment, has sights set on growing personal spending in the U.S.
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Another Israeli company is Nasdaq-bound. Home Skinovations, founded by Moshe Mizrahi, manufactures laser hair-removal devices. It joins Kamada and Babylon, other Israeli companies planning on joining Nasdaq. The company, which is not traded on the Tel Aviv Stock Exchange, presented a confidential draft prospectus for an initial public offering aimed at raising $75 million-$80 million on Nasdaq at a company...
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HIST 032 at Mills College
American History II
2 ratings
Reviewed on
Jun 7, 2011
Is this helpful?
Yes No
This course is very interesting and and simple class to take. The instructor (Professor Issel) is very kind and has a lot of knowledge reguarding the American History period he covers. This class is offered at an early time and this professor lectures off of powerpoint presentation, so it can be a lot to handle at an early time. But overall, Issel makes the course easy. There are only 2 essays required as projects for the whole semester, and each midterm are essays.
Reviewed on
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This course was very interesting and this textbook helped greatly.


text:
Capil Villas
from £81 /night help Price for guests, Nights
from £81 /night help Price for guests, Nights
Estimated nightly price based on a weekly stay. Excludes fees (if applicable). Enter your dates to see the total cost.
Villa / 3 bedrooms / sleeps 8
Availability Your dates are available
Villa / 3 bedrooms / sleeps 8
|Key Info
Welcome to Capil Villas. This beautiful villa is situated in a quiet lane in the heart of Seminyak. All bedrooms have private en suite facilities, the master bedroom has an additional dressing room. Open plan livingroom and kitchen area and all bedrooms have air conditioning or fan options. Flat screen tv's in the living area as well as the bedrooms. Located a few minutes walk from Bintang supermarket and restaurants, shops and cafes that the area is known for. Walking distance to double six beach and the beach side restaurants.
|Sleeps up to 8, 3 bedrooms
|Car advised
|Nearest travel links
|Nearest airport: Ngurah Rai Airport
|Family friendly
|Great for children of all ages
|No pets allowed, No smoking at this property
Features and Facilities
|Internet access, DVD player, Staffed property
|Private outdoor pool (unheated)
|Air conditioning, TV, CD player, Safe, Satellite TV, Wi-Fi available
|Kettle, Toaster, Hair dryer
|Cooker, Microwave, Fridge, Freezer
|3 bedrooms, 3 bathrooms of which 3 En suites
|King Beds (1), Double beds (2), Dining seats for 6
|Linen provided, Towels provided
|Private outdoor pool (unheated), Private garden
|Parking, Not suitable for wheelchair users
The Bali region
When looking on google maps- if looking via street view, the construction is completed and is not noisy.
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40% Response rate
Calendar last updated:26 Jun 2015
Based in Indonesia
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Will this cable enable you to use the Mid 2010 iMac with Mini Display Port as a display for the new MacBook Pro with Thunderbolt in clam shell mode?
- Asked by Tuan L from Austin
Apple Thunderbolt Cable
Product No Longer Available
1 Answer from the Community
While this should work, it would be more affordable to purchase a regular miniDP cable to achieve what you are inquiring.
- Answered by Marcus V from Temple City


text:
I'll start... BTW, in the Arroyo pics I think I got the back of TB and didn't know it at the time!
1st pic: Lifesize team photo display - you could go in between the rows and have your picture taken.
2nd and 8th pics: Row of hats displaying teams and their minor league affiliates.
3rd pic: Doubleday Field
4th and 5th pics: Phillips
6th pic: Cheerleaders
7th pic: Replica of the Reds locker room (this was beside the team photo display).
9th and 10th pics: Arroyo and Claussen


text:
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Make plans to spend 2 or more nights during the week with us and you'll receive 10% off your total stay!
Stay Dates are November 3rd, 2014 - January 30th, 2015 - Weekends and Special Holidays are excluded.
* 2014-2015 Blackout Dates do apply. Other rates may be available! Please call us directly at 512-467-6000 to ask about current availability.


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|3219 Series Coffee Table with 2 Ottomans
|19" H x 50" W x 30" D
|106.49 lbs
|3219 Series End Table
|23" H x 24" W x 24" D
|33.87 lbs
|3219 Series Console Table
|30" H x 50" W x 18" D
|70.84 lbs
|Product Category:
|Coffee Table Sets
Questions & Answers
Woodbridge Home Designs 3219 Series Coffee Table Set
Woodbridge Home Designs 3219 series Coffee Table with 2 Ottomans
Felicita from Norwich, CT– Verified Buyer– Top 1000 Reviewer
I love the way my table looks in my dinning / living room combo. It took a while for my replacement glass to arrive. But it look beautiful and I love it.
as pictured,
Careful Shopper from Queens, NY– Verified Buyer
Product looks pretty, but be prepared with a touch-up marker to fix up visible spots where wood is not finished properly. My husband put this together pretty fast, but he plans on solidifying it with extra screws to hold the bottom wood V together so that it is more sturdy. If you aren't too picky[...]good for the price.
Fine Piece of Furniture
Doug MacDonald from The Villages, FL– Verified Buyer
The table was easy to assemble and is a well designed, solid piece of furniture. I plan on having a 50 inch plasma TV mounted on the wall over the table displaying wall art. The laptop computer or other small equipment to control the pictures being presented on the TV will sit on the table. The chair makes it convenient to make changes to the controlling equipment as the presentations will probably be a lifetime project.
Series Console Table
J. from NV– Verified Buyer
This console table is great for a vanity. Goes right against the wall, it's small, the chair goes in so it's not in the way. Got all my make up set up on it and I love it!
Price is right
Condo living from Calgary, AB
Found that the wood is a little soft as mentioned in other posts. Love the table though. Live in a condo and it was the perfect way to have a coffee table beside the couch, an additional chair, and display some vases. Price is right. Would recommend to a friend.
Product is lovely
Veronica from Canada– Verified Buyer
The sofa table is exactly what we wanted. [...] I really don't know who to repair it so I will have to cover it with similar colour. I do not want to return it for another one. That is just too much hasle.
Changing my mind
condo from Calgary, AB
I wrote earlier in the post called "Price is Right". I take that back. The product is poor quality. The wood has shrunk so the glass no longer fits in the top inset. I use a humidifier in my condo so I don't understand. [...]Wood is cheap. It is cork board underneath. DO NOT BUY THIS TABLE. [...]
Wood too too Soft No pets or kids!
Nicole from FL
I had to order 2 replacement parts and the wood is so soft...no pets or kids or it won't last a week! It looks nice though[...]. Dont tighten the screws a lot or soft wood will crack!


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Men's VIP List
Both Women's & Men's VIP List
J BRAND embodies modern classics with a masculine fit. Whether you're looking to rock some killer cargos, a simple five pocket twill and distressed jean or a clean dark denim J BRAND's got you covered. And if you tend to shy away from a fancy pocket design J BRAND is perfect for you as the provide fashion with a minimum of the unnecessary. Don't just take our word for it Brad Pitt, Gerard Butler, Zac Efron, Taylor Lautner, Bradley Cooper, Ben Affleck and Channing Tatum count themselves among J BRAND's many fans. Their styles take you from the street, to the beach to your favorite watering hole and rock 'em with your best kicks, havaianas or boots.
Want to look like Jay-Z, Kanye West, and/or Kid Cudi? Hi-Tops are their jam and you can pair these kicks with just about anything. An easy shirt and tie combo with a solid monotone Supra hi-top, will have you ready for a club and the office. Then of course they work super-cool with dark denim and a hoodie. Just ask Justin Bieber; that's his go-to move. Feeling like a cable knit sweater day? Then get your Drake on and pair it with these sneakers from Supra.


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Suit claims defendants failed to perform duties related to residential mortgage-backed securities.
Colorado regulator approves charter for Fourth Corner CU, set to open Jan. 1.
The NCUA accuses DB of failing to meet trustee obligations when it sold bad securities to failed corporates.
The NCUA released two videos Sept. 16 to help senior citizens identify and prevent fraud.
Alerts follow NCUA Chairman's Matz 2013 letter encouraging credit unions to review fraud, financial abuse polices.
A credit union lawyer weighs in on a measure that could level the playing field with banks.
Susan Carcieri's original conviction for a staged robbery was overturned on a technicality.
Trailblazer Outstanding Political Action winner, the $822 million Credit Union ONE, fought skimmers by spearheading new state legislation.
Trailblazer Outstanding Political Action winner, suburban Detroit's Credit Union ONE, fought skimmers by spearheading new state legislation.
A second credit union files a lawsuit against the Minneapolis-based retailer over massive data breach.


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Highland Teachers End Strike
Classes resume Friday
Highland Teachers, District Resume Negotiations
The Highland teachers union and school board were set to meet Thursday to hammer out a three-year contract agreement that could end an ongoing teacher strike.
Highland Teachers Reject Contract
Strike continues, as Sunday's vote on tentative agreement wasn't even close.
Highland School District Teachers Go on Strike
Teachers in a southwestern Illinois' Highland School District went on strike Thursday, shutting down the schools as part of a labor dispute.
Teen Dies After Corvette Crash in Highland
A teenager has died following a single-vehicle crash Friday evening in rural Highland.
Guilty Plea in Highland ATM Robbery
Michigan man admits holding up Bradford National Bank worker.
Highland Teen Visiting Mizzou Died of Enlarged Heart
Medical examiner's report released on Gregory Holthaus case
Highland, Ill., Perryville, Mo. Cancel Trick-or-Treating
"We've had some complaints come in," Highland Police Chief Terry Bell says. "We've also had some people praise us for looking out for the kids."
Belleville Martial Arts Instructor Admits to Sexual Abuse
Christopher Horton, 22, of Highland entered pleas to five counts of sexual exploitation of a minor and one count of attempted sexual exploitation of a minor.
Randolph County State's Attorney Will Allow Concealed Carry
The decisions by some legal officials in Illinois come in the wake of a U.S. Court of Appeals decision that requires Illinois lawmakers to create concealed-carry legislation awaiting Gov. Quinn's signature.


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Mentally and physically, I am healthier than I have ever been. At 61, I feel like I'm continuing to grow and evolve! Life just seems to keep getting better.
I currently have an important person in my life, but we both understand that we are not each other's primary partner. So, I am looking for my beloved. If you and I make a strong connection, I am open to exploring with you which relationship model fits for us both - monogamy, polyamory, monogamish - I open to exactly what feels right for us in the moment. If we truly are meant to be, there will be no obstacle we can't overcome, as long as we are using direct, gentle and loving communication!


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Game Stats
Game Stats
W: S. Marcum (12-5) L: J. Washburn (9-12)
S: J. Accardo (26)
|1st Inning
Beltre singled to shallow left center, Suzuki scored, Ibanez to second.
|2nd Inning
McDonald tripled to center, Glaus and Overbay scored.
|3rd Inning
Adrian Beltre (21) solo shot to left center off Marcum.
|3rd Inning
Troy Glaus (18) 2 run shot to left center off Washburn, Rios scored.
Lyle Overbay (10) solo shot to right off Washburn.
|4th Inning
Alex Rios (22) solo shot to left center off Washburn.
|5th Inning
Jose Vidro (6) 2 run shot to right off Marcum, Suzuki scored.
|8th Inning
Johjima doubled to deep left center, Ibanez scored.
|8th Inning
Thomas singled to center, Rios scored.


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SSodapocalypse: Is There Room for Common Sense in the Soda Debate?
There's a can of soda in the vending machine down the hall biding its time, waiting for the perfect moment to strike.
Okay, that's probably a stretch, but soda and energy drinks are coming under heavy fire, from New York City mayor Michael Bloomberg's attempt to ban large-sized sodas to a new, cataclysmic statistic that paints soda as a serial killer.


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Definition from Wiktionary, the free dictionary
From Middle French friction and directly from Latin frictionem, nom. frictio ("a rubbing, rubbing down")
friction (uncountable)
- The rubbing of one object or surface against another.
2013 July-August, Henry Petroski, "Geothermal Energy", American Scientist, volume 101, number 4:
- Energy has seldom been found where we need it when we want it. Ancient nomads, wishing to ward off the evening chill and enjoy a meal around a campfire, had to collect wood and then spend time and effort coaxing the heat of friction out from between sticks to kindle a flame.
- Conflict, as between persons having dissimilar ideas or interests; clash.
- (physics): A force that resists the relative motion or tendency to such motion of two bodies in contact.
- 1839, Denison Olmsted, A Compendium of Astronomy Page 95
- Secondly, When a body is once in motion it will continue to move forever, unless something stops it. When a ball is struck on the surface of the earth, the friction of the earth and the resistance of the air soon stop its motion.
- 1839, Denison Olmsted, A Compendium of Astronomy Page 95
Related terms[edit]
- coefficient of friction
- static friction
- dynamic friction
- friction clutch
- friction match
- frictive
- frictional
- frictious
The rubbing of one object or surface against another
A force that resists the relative motion or tendency to such motion of two bodies in contact
- The translations below need to be checked and inserted above into the appropriate translation tables, removing any numbers. Numbers do not necessarily match those in definitions. See instructions at Help:How to check translations.
Translations to be checked
See also[edit]
From Latin frictionem, nom. frictio ("a rubbing, rubbing down")
friction f (plural frictions)
External links[edit]
- "friction" in le Trésor de la langue française informatisé (The Digitized Treasury of the French Language).
- English terms derived from Middle French
- English terms derived from Latin
- English terms with IPA pronunciation
- English terms with audio links
- English lemmas
- English nouns
- English uncountable nouns
- en:Physics
- en:Mechanics
- French terms derived from Latin
- French terms with IPA pronunciation
- French lemmas
- French nouns
- French feminine nouns
- French countable nouns


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Live updates
Yeovil women join thousands on Moonwalk
Thousands of people, including hundreds from the West, have taken part in one of the country's biggest charity walks.
Saturday night's moonwalk took place in London with walkers wearing the trademark brightly coloured bras. They raised £3.5 million to help tackle breast cancer.
Three women travelled from Yeovil in memory of friends and family....
Life after breast cancer surgery
A charity calendar has been made to show a mastectomy can be a positive experience.
Across the West Country one in 8 women will be diagnosed with breast cancer in their lifetime, and those who find out they carry the breast cancer gene may choose drastic surgery to reduce their risk.
But as David Wood reports, one group of women has turned it into a life-affirming opportunity.
Revolutionary treatment for breast cancer sufferers
A new way of prescribing a cancer drug, which was tested in Cornwall, is now available to every NHS trust in the country.
Herceptin is described as a revolution in breast cancer treatment; an injection which dramatically reduces the time that patients have to spend in hospital. Experts in Cornwall are helping to pioneer this new way of administering the drug. Our health correspondent Jacquie Bird reports
Faster treatment for breast cancer patients
Some breast cancer patients in Cornwall could benefit from faster treatment from today. The drug Herceptin can now be given by a quick injection rather than a much longer intravenous drip. It follows trials among patients at the Royal Cornwall Hospital.
- Duncan Sleightholme
Mother recovering after pioneering op in Plymouth
A young mother is recovering after a pioneering operation at Plymouth's Derriford Hospital, using pig skin as part of reconstructive surgery. Kelly Cruse from Plymouth chose to have a double mastectomy to avoid the risk of developing breast cancer in the future.
- ITV Report


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Home » Courses » All Jobs for MCA
Experienced software engineers are required for VB.NET and ASP.NET development. Walk in directly to the below address with your resume.Vyapin Software Systems #48/43,12th Avenue,K.G.Sunshine,Ashok Nagar,Che-83.Time:10.30 AM to 12 PM. Exp:.6 to 2yrs
We at Dharani Info Technologies Pvt. Ltd. are seeking freshers who are willing to have a career in IT, Having thirst for knowledge, Desire to learn on the job and to work in challenging environment. Company Profile We develop and market our own brand of innovative mobi...
Microsoft VBScript runtime
Out of stack space: 'StripHTML'
/include/helperMethods.asp, line 509


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This is a double stamped X-out Champion Glow Aviar from the 2011 Seth Burton Memorial. The disc is practically flawless. I suspect it was x`ed out because of what feels like a few specs of sand on the surface near the edge. These are very, very slight and will not affect the performance of the disc.
These are stiff and flat with a high shoulder. Very bright glow material.
Black and violet foil double stamp.
175 grams.
Community Poll


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You can now invite anyone to meet at your favorite Starbucks.
Limited-time feature
38 year old man | Atlanta, GA, USA | Seeking women 25-38 within 50 miles
Active within 24 hours
I'm the king of useless information..might as well just put that out there now!
Well as I'm waiting for the comedy gods to write my profile (figured Conan O'Brien might pitch in now that he's slumming it on cable) I'll just go ahead and write something myself...just in case that I don't hear back from Jon Stewart or Will Ferrell either! I'm a tall guy who likes to travel...actually make that loves to travel...something about stepping outside the airport to somewhere new has always captivated me. I just got back from an unforgettable two weeks in Spain. In a strange way I guess I can thank Mother Nature for sending tornadoes and floods that get me sent out for work and land me frequent flier miles...so yay disasters! I also went on a fellowship program to Germany and Belgium a couple years ago, and discovered how great Berlin is. Originally from Phoenix I moved to Atlanta not knowing a soul, and something must be going right because i'm still here. It's been a sacrifice to a degree because I have a great family back in Arizona, fortunately they've supported me in my quest to advance my follow my career here in Atlanta. Outside of work I'm either drinking the aforementioned cocktail, or i'm golfing, hiking, road tripping, playing poker, or hanging out with my great friends that i've made in my time here. I'm also on the local volunteer board for St. Vincent de Paul. As for what I'm looking for, I would like to get to know someone educated who is also into travel, is close with family, and definitely likes to stay active!
Alumni connections , Cooking , Dining out , Movies/Videos , Museums and art , Music and concerts , Exploring new areas , Nightclubs/Dancing , Performing arts , Playing sports , Political interests , Travel/Sightseeing , Watching sports , Wine tasting
Baseball, Bowling, Football, Golf, Other types of exercise, Skiing, Soccer, Swimming, Walking / Hiking, Weights / Machines
I exercise 5 or more times per week.
I like Dogs
Middle of the Road
My beloved hometown of Phoenix, Grant Park, Inman Park, Chile, Croatia
Big fan of "Entourage" "Boardwalk Empire" "Man v. Food" CNN, music wise i'm all over the map -- listen to more 80s than the average fella.
Braves games, golf, poker, travel, volunteer
Seven Habits of Highly Effective People...a news wire or press release
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What he is looking for
|6'3" (190cms)
|3'0" (91cms) to 8'11" (271cms)
|Body type:
|About average
|No preference
|No preference
|Dark brown
|No preference
|No Way
|No preference
|Social Drinker
|No preference
|Other profession
|No preference
Inform the world, one minute and twenty seconds at a time (in the broadcasting world)
|I'll tell you later
|No preference
|Never Married
|No preference
|Have kids:
|Wants kids:
|Definitely, Someday, Not sure, Probably not
|White / Caucasian
|No preference
Chikonky - half chicano, half honky
|Christian / Catholic
|No preference
Half-Mexican - comes with the territory I suppose
|English, Spanish
|Bachelors degree
|Bachelors degree, Graduate degree, PhD / Post Doctoral


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Constitution of the Republic of Macedonia
From Wikipedia, the free encyclopedia
|This article needs more links to other articles to help integrate it into the encyclopedia. (December 2012)
|This article is part of a series on the
politics and government of
the Republic of Macedonia
The Constitution of the Republic of Macedonia is a codified constitution outlining the country's system of government and basic human rights.
In 2001 it was announced that Macedonia had adopted a new Constitution which enshrined 15 basic rights and has granted rights to the country's ethnic Albanian population, as part of the Ohrid Agreement.[1][2]
- ^ BBC NEWS | World | Europe | Macedonia adopts new constitution
- ^ Macedonia to alter constitution for Albanians | World news | The Guardian
External links[edit]


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Whatfer over wet fur leads to fisticuffs
Bob McPhail 10:30 a.m., July 6
Not following anyone yet
Bob McPhail 10:30 a.m., July 6
Walter Mencken 9:53 a.m., July 6
Barbarella Fokos 8 a.m., July 6
Various Authors 10:39 a.m., July 5
Walter Mencken 9:44 a.m., July 5
Daniel Powell 8 a.m., July 5
© 2015 San Diego Reader. All rights reserved. No part of this site may be reproduced without our written permission.
Each newsletter subscription means another chance to win!Close


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Heatwave Refrigeration and Air Conditioning, Inc.
Heating and Cooling in Tucson, Arizona
When looking for HVAC services near Tucson and Oro Valley, Arizona, it can be difficult to find a company dedicated to quality repairs and service. You can rely on our HVAC company for affordable and honest repairs. Call us at (520) 329-4131 for 24/7 emergency heating and cooling service.
Here in Arizona, broken air conditioning can be extremely uncomfortable. Once you call us to fix your air conditioner, our HVAC company will be there as soon as possible to get you and your family or business comfortable and cool again. We work with all types of central air systems including heat pumps and evaporative coolers.
"The Difference Between Good Enough and The Very Best"
You'll never worry about a repair job from us as we provide you with both experience and knowledge to ensure your equipment works like it should. With personalized service, you always know exactly what is going on.
While some people might think that Arizona never gets cold, residents truly know that it can be downright chilly at times. With heating repair from our HVAC company, you can be guaranteed great service. We complete heating and cooling services for mobile homes.
If you need a replacement heating or air conditioning unit installed our team has the tools and expertise to get the job done.
For AC installation and heating repair, choose Heatwave Refrigeration and Air Conditioning, Inc. in Tucson, Arizona. Our team is dedicated to honest and experienced heating and air conditioning service, and we look forward to working with you. Please contact us to schedule your air conditioning repair.
Our Office Hours are listed below, 24 hour service is available 7 days a week.


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Lucky 13
Bear Tooth becomes a teenager this week, as the Spenard hot spot celebrates its 13th anniversary Thursday. The party starts 9 p.m., with music by Minnesota pop-rockers Motion City Soundtrack. Tickets are $30 (21 and older). Visit beartooththeatre.net for info.
Making history
Last year, the now-defunct Boston Phoenix called Historian the best new band in Alaska, and the self-described "doomwop" band's follow-up to the "Dream Crusher" EP is due sometime this summer. In the meantime, the group will release the new single "Rebellious Flesh" as a download code on limited-edition posters designed by singer Nate Hurst. The code also gets you a remix of "All My Friends Are Extinct" by Alex the Lion. Grab a copy at the show, 9 p.m. Saturday at the S Lounge with Turquoise Boy and Ghost Hands, $7 (21 and older), and stream the single at adn.com/playblog.
Beer and Barley Wine
Tap Root hosts its third annual Spenard Beer and Mead Social on Saturday. There are two sessions in which to sample beverages from Alaska-based breweries, meaderies and distilleries: noon-3 p.m. or 4-7 p.m. Tickets are $30 (21 and older) and include admission to the Melissa Mitchell show later that night. Visit taprootalaska.com for info.
Anchorage Daily News


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I have always loved basketball and im alright at it, but ive never been on the school team. My school only won 2 games this season. I had a chance to be on the team this year but didnt take it and now im thinking i want to do it next year as i will be a senior. This summer I'm making a major push to vastly improve my game, any tips or advice? much appreciated
Ihoops can prob. help. Ask some of ur friends if they want to help ya. tell them to not hold back their skill or you wont get better. Heres some good advice I got from a Coach, " If practice is harder than the games the games will come easy" hope it helps!
yeah, i always stay up to date on everything on ihoops
thanks and thats really good advice by your coach


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College of Agriculture
The field of Food Science applies science, such as microbiology and biochemistry, to discover ways to improve the taste, nutrition, and value of the food supply. A food scientist possesses the skills necessary to convert raw food products into safe, attractive foods and beverages. Graduates apply scientific knowledge and economic principles to food production, storage, distribution, product development, quality control, inspection, and sales, or they, pursue graduate studies in food processing, microbiology, or chemistry.
Transfer GPA and Course Requirements
Purdue admits to individual majors. To be considered for admission as a college transfer student, applicants must meet minimum GPA requirements for their desired major. In addition, some majors have course requirements. Requirements for this major are posted below (unless the program is closed to transfers).
Minimum GPA: 2.5
Contact Information
Food Science
Phone: 765-494-2766


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Hewlett-Packard Fined $58.7M After Pleading Guilty To Bribing Russian Officials For Contract
Hewlett-Packard has pleaded guilty to felony charges that former employees bribed Russian government officials for a contract, and the company has been fined $58.7 million.
Hewlett-Packard Agrees To Pay $108 Million Penalty To Settle Foreign Bribery Charges
Hewlett-Packard Co. and its Russian, Polish and Mexican subsidiaries agreed Wednesday to pay $108 million in penalties to settle criminal and civil charges of paying bribes and illegal commissions to secure foreign government contracts.
Woman Accused Of Offering Rape Victim $30K Not To Testify In San Jose Case
A San Jose rape case took a bizarre turn when a woman was arrested in the middle of the trial on suspicion of flying to Detroit and offering the victim $30,000 not to testify.
California Claims Drug Giant Bribed Docs To Prescribe
A whistleblower lawsuit claims Bristol-Myers Squibb Co. bribed doctors to prescribe its drugs, costing insurers perhaps millions of dollars in the largest alleged health care fraud case ever handled by the state.


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Darren Criss at the MusicMusic Video Awards 2012 at Toronto, Canada on June 17, 2012.
It seems like every single one of Taylor Swift's best friends seriously can't get enough of her.
I once spent my Friday night stalking Chrissy Teigen's mom.
You know it's a going to be a good week when Chrissy Teigen is getting naked on a Monday.


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The Mellman Group conducted a survey of 500 registered voters in Virginia, who were interviewed by telephone January 22-24, 2008. The margin of error for this survey is +/-4.4 percent at the 95 percent level of confidence. The margin of error is higher for subgroups.
|SOURCE Campaign for Tobacco-Free Kids
Copyright©2008 PR Newswire.
All rights reserved


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Results 1 to 3 of 3
- Join Date
- Jul 2003
- Posts
- 5,529
Posted On:
8/11/2004 2:37pm--
Kickboxing at Battle of Atlanta (email)
Joe Corley announced today the addition of PKA KICKBOXING, the WORLD SUPER HEAVYWEIGHT CHAMPIONSHIP to the main event lineups for the BATTLE OF ATLANTA September 10 & 11. All the information has been added to the www.battleofatlanta.com site.
Atlantas Mark Selbee (64, 215 lbs. 20-0, 18 KOs and #1 World Heavyweight contender) will be facing Montreals Raoul Doucet (65, 225 lbs. 14-2-1, 7 KOs and #1 World Super Heavyweight contender) for 12 rounds of PKA KICKBOXING to fill the vacant IKF World SuperHeavyweight title, Master Corley explained.
What a great place to entertain and "train" your friends and students!
The Battle of Atlanta has been the breeding ground for many of our worlds greatest champions, from Bill Superfoot Wallace to Joe Lewis and Jeff Smith, reported PKC president Glenn Keeney, and has been the home of some of the most historic kickboxing matches of all timefrom the first title defense of Corley vs. Wallace, Smith vs. Slocki, Rhome vs. Hefton, Theriault vs. Thurman and where Roufus won his first world title. Atlantas Mark Selbee and Canadian Raoul Doucet should make for this same kind of excitement. With 450 pounds of black belt intensity, 37 wins and 25 knockouts between them, it should be a BATTLE OF ATLANTA classic knockout event!
This matchup is part of a double main event the other half of which features our PKA WORLD POINT FIGHTING CHAMPIONSHIP, Master Corley added. NASKA has now rated the top ten fighters in the country based on their head-to-head results over the past year(s), and they are every bit as dynamic as their predecessors of yesteryear. They will be joined by 6 Battle of Atlanta champions and fight down this night to the BEST OF THE BEST!
Speaking of the BEST, Atlantas travel expert Lynn Gregory suggests that you go to www.airtran.com and www.delta.com for the best airfares available. Its a great one day sale, with fares as low as $49, she reports. Check it out and make your reservations for special Battle hotel rates as well on line at the Battle site (look under Quick Facts and save BIG $$ per night at Hyatt Regency Atlanta).
Call 770-998-4610 for more information or Email email@example.com.
Last edited by blankslate; 8/11/2004 2:40pm at .
1% Shark is better than you.
- Join Date
- Sep 2003
- Location
- Atlanta GA
- Posts
- 9,167
Posted On:
8/13/2004 1:13pm
- Join Date
- Jul 2003
- Posts
- 5,529
Posted On:
8/13/2004 1:15pm


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Learn more about Eternity Heart CZ Gem Solitaires 14K Yellow Gold Reverse Navel:
Manufacturer: FreshTrends
Mfg Part#: FT-YGN-32
Sku: 228733959
See more in Body Piercings
|A best-selling gift, this beautiful classic Eternity belly ring represents the Past, Present and Future. This belly button ring is wonderful if you are looking for a more classic and sophisticated style of body jewelry. The belly ring is crafted entirely from nickel-free, solid 14K gold and has a 4mm solid gold top ball. Barbell Size: 14G (1.6mm) Barbell Length: 7/16" (11mm)


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Ben Hamper
|Ben Hamper
Hamper at home
|Bernard Egan Hamper III
Flint, Michigan, United States
Bernard Egan "Ben" Hamper (born c. 1956) is a Michigan-based writer. He was born in Flint, Michigan from a family that had many former employees of General Motors amongst its members. Hamper also worked for General Motors in Michigan for several years and wrote for Michael Moore's Flint Voice. He has also worked as a correspondent on several of Moore's television projects. Ben also hosted and wrote comedy for Take No Prisoners TV show in Flint. This program aired on local community access and documented the Flint underground music scene from 1989 to 1998.
In 2006, Hamper launched a new radio show, Soul Possession, on community radio station WNMC-FM in Traverse City, Michigan. The show focuses on his extensive collection of obscure soul and funk records and can be heard Friday evenings between 9 and 11 pm ET via the station's audio stream. In 2010, Hamper launched another radio show, Head For The Hills, also on WNMC, focusing on his obscure collection of classic and obscure Country records and can be heard Sundays between 10AM and 12PM ET.
His memoir, Rivethead: Tales From the Assembly Line, published in 1991, is an autobiographical account of his life in Flint and subsequent employment on the General Motors assembly line between 1977 and 1988.
Television and film[edit]
Hamper has appeared in a number of high-profile TV and film roles, most notably in association with Michael Moore. In fact Hamper was at Moore's side for most of Moore's career from his very early days to his TV shows in the mid 1990s.
Hamper first began writing articles for the Flint Voice. In fact, on the day Moore and Hamper were to meet to discuss Hamper's writing for the Flint Voice, Harry Chapin — a long time benefactor for the paper — was killed in a car accident. Hamper turned around and went home. He did however end up with a writing assignment and rather quickly became a local celebrity who wrote scathing true stories of life on the assembly line. He was kept on when the Flint Voice became the statewide Michigan Voice where he was again one of the more popular writers. When Moore left for Mother Jones in 1986, he brought Hamper over with him and put him on the cover. Moore was fired shortly after. Hamper was asked to keep writing for Mother Jones, but out of loyalty chose not to continue {Rivethead: Tales from the Assembly Line, pg 220}.
When production of Moore's documentary film Roger & Me began in early February 1987, Moore asked Hamper to recall one of his infamous panic attacks stemming from his work at the GM Truck & Bus plant on Van Slyke Road.
After Roger & Me, Hamper's book Rivethead became a national bestseller. He then appeared on the cover of The Wall Street Journal and was interviewed by NBC and CBS for various news shows.
Matt Dillon was tapped to star in the film adaption of Rivethead, with Richard Linklater writing and directing, but the project did not move beyond early stages of development.
In 1995, Hamper had a memorable cameo appearance in Michael Moore's film Canadian Bacon and was later tapped as a correspondent for both TV Nation and The Awful Truth documentary television shows. These were the last official associations with Moore, but the two remain good friends to this day.[citation needed]
Further reading[edit]
- Tim Yohannan, "Michael & Me: The Ben Hamper Story," Maximum Rocknroll, whole no. 136 (Sept. 1994), pp. 104–107.
External links[edit]
- Hamper's homepage
- Ben Hamper at the Internet Movie Database
- Ben Hamper's Chevrolet Truck & Bus ID badge at FlintHistory.com
- Hamper on TV Nation
- Hamper profile at WNMC
- Ben Hamper's Radio Show archive page


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A123 Systems runs out of cash and sells assets for $125 million
You may not recognize the name A123 Systems. The company is a manufacturer and designer of batteries and battery packs for the electric vehicle market. A123 Systems may be best known as the battery manufacturer for the Fisker Karma hybrid.


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Get a new Microsoft Office tip every Tuesday. Take a five-minute break to improve your productivity and efficiency.
Ensure that everyone can access, use, and benefit from your Microsoft Office documents by implementing these accessibility best practices from David Rivers.
Take a look at suite-wide enhancements like cloud integration, Touch Mode, PDF editing, and Ribbon customization, as well as individual app improvements added to Office 2013.
"There are quite a few things that make lynda.com the best online learning platform. One of the greatest is that you guys listen and respond to your audience and I can't thank you enough for doing so." —Nathan
more from our members »


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Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.
A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.
A total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.
We found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol.
Keywords:Human leukocyte antigen; severe cutaneous reaction; Stevens-Johnson syndrome; toxic epidermal necrolysis; allopurinol; meta-analysis
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe manifestations of cutaneous hypersensitivity reactions affecting approximately 0.4 to 6 persons per million populations each year [1-3]. Despite the low incidence, the mortality rate has been estimated at 5% for SJS and 30-50% for TEN [2,4,5]. Clinical presentation of SJS and TEN is characterized by a rapidly progressing, blistering exanthema accompanied by mucosal involvement and systemic symptoms that may present as fever, mild elevation of hepatic enzymes, intestinal and pulmonary manifestations [6].
Medications are thought to be a major cause of SJS/TEN cases (~80%). Chemical exposures, mycoplasma pneumonia, viral infections, and immunizations have also been implicated [2]. Iatrogenic causes that have been firmly correlated with both SJS and TEN syndromes include: antiepileptic drugs, antibiotics, and uric acid lowering agents [2,5]. A multinational case-control study recently reported that allopurinol, a xanthine oxidase inhibitor commonly used to treat hyperuricemia and gouty arthritis, was the most frequent drug associated with SJS and TEN [7].
The pathogenesis of allopurinol-induced SJS and TEN is consistent with a delayed-type immune-mediated reaction [2]. The pathogenesis, in conjunction with observed familial predispositions to allopurinol-induced SJS/TEN, alludes to potential genetic-based immunological markers [8]. A number of gene-association investigations have been conducted to elucidate the genetic component of allopurinol-induced SJS/TEN. Results from these studies suggest a strong association with the human leukocyte antigen (HLA), HLA-B*5801 [9-15]. However, these previous studies have shown considerable variation among the magnitude of the association between allopurinol-induced SJS/TEN and HLA-B*5801. A major limitation of the individual studies stems from the low incidence of allopurinol-induced SJS/TEN, which generates observational studies with relatively small sample sizes and insufficient power.
Given the recent accumulation of genetic association studies, inconsistent results, and inadequate power, a quantitative synthesis of the evidence is warranted. The objective of this review is to systematically accumulate and quantitatively analyze the genetic association between HLA-B*5801 and allopurinol-induced SJS/TEN, as well as to elucidate any between-study heterogeneity.
Data sources and search strategy
We performed systematic searches on the following databases: MEDLINE, PreMEDLINE, Cochrane library, International Pharmaceutical Abstracts (IPA), Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), World Health Organization (WHO) International Clinical Trial Registry, and ClinicalTrials.gov from its inception until June 2011. The search terms used were "HLA-B" OR "Human leukocyte antigen" with AND "allopurinol" AND "Stevens Johnson Syndrome" OR "Toxic Epidermal Necrolysis" OR their acronyms. The Medical Subject Headings (MeSH) was employed when searching database with such option available. Language of the published papers was not restricted and only human studies were included. Bibliographies of the included articles were examined to identify additional studies.
Study selection
Two reviewers independently evaluated titles and abstracts retrieved from the comprehensive searches for inclusion. Disagreements were resolved by group consensus. To be included, studies were required to meeting the following criteria: 1) investigated the association between HLA-B*5801 and allopurinol-induced SJS/TEN; 2) reported data sufficient for calculating carrier frequency of HLA-B*5801 among cases and controls; 3) cases were subjects that were defined according to detached body surface area as SJS (< 10%), SJS/TEN overlap (10-30%) and TEN (> 30%) [16-18]. Animal studies, case reports, review articles, and duplicate studies were excluded.
Data extraction and quality assessment
All articles were extracted independently by reviewers (RS, EEE), and discrepancies were resolved through discussion. The following data were extracted from each study: study design, eligibility criteria, diagnostic criteria of SJS or TEN, selection of cases and controls, patient demographics, genotyping technique, and main results. We used Newcastle-Ottawa quality assessment scale [19] for assessing the quality of included observational studies in this review.
Data analysis
The overall odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to determine the association between the presence of HLA-B*5801 in at least one allele and allopurinol-induced SJS/TEN. In some studies [11,12], allele frequency data were presented. Based on a study of Tanaka et al [20] and database of Major Histocompatibility Complex [8], we converted allele frequency data into the number of patients with HLA-B*5801 present in at least one allele. All analyses were performed using DerSimonian and Laird method [21] under a random-effects model. Sensitivity analyses were also performed to determine the robustness of the findings by ethnicity. The analyses were also performed separately for those using different types of control groups (e.g. controls obtained from the study, controls obtained from the population database). Statistical heterogeneity was assessed via the Q-statistic and I-squared tests [22]. A Q-value of 0.10 indicated statistically significant between-study heterogeneity and I-squared values < 25% denoted no/minimal heterogeneity across studies. Begg's test and Egger's test were used to evaluate the publication bias [23,24].
Study selection
A total of 94 articles were identified. After exclusion of duplication (6 articles), review articles or case reports (59 articles), non-human studies (1 article), studies in which patients did not receive allopurinol (5 articles), studies which did not examine the association between HLA-B*5801 genotype and SJS or TEN outcomes (14 articles) and studies which did not have comparator (3 articles), 6 remaining studies included in the meta-analysis [10-15] (Figure 1). No additional articles were identified via review of the bibliographies of included studies.
Figure 1. A flow diagram for study identification, inclusion and exclusion.
Study Characteristics
Characteristics of included studies are summarized in Table 1 and Table 2. All studies [10-15] included 96 SJS/TEN cases, 678 matched-controls and 3378 population-controls. The reported average age was 57.4 years old (range from 50.0-70.9 years) [10-15] and 51.6 years old (range from 35.9-63.5 years) [10,13-15] for cases and matched-control, respectively. Most patients were men (58.3% for cases and 77.7% for matched-controls). Kaniwa et al [11] and Lonjou et al [12] did not report gender percentage and mean age in the control groups.
Table 1. Characteristics of studies included in the meta-analysis
Table 2. Patients' demographic information
All SJS/TEN cases in all 6 studies were diagnosed according to the consensus definition [16-18]. All cases required confirmation of diagnosis by dermatologist [10,13], allergy specialist [15], Japan Severe Adverse Reaction (JSCAR) research group [11], or RegiSCAR expert committee [12]. All studies, except Kaniwa et al [11], required specific criteria for allopurinol exposure for the case definition. They included the duration of exposure to allopurinol no longer than 42 days [12], 60 days [15], or 3 months [10,13], and improvement of symptoms after drug discontinuation [10,13]. Hung et al [7] was the only study specifying that patients without symptoms upon re-exposure must be excluded. Despite a requirement of being exposed to allopurinol of cases, three studies [11-13] reported no information on dose of allopurinol and four studies [10,13-15] did not reported the actual duration of allopurinol exposure in both cases and controls.
Three studies [10,13,14] employed classical case control approach in which controls were matched on hospital. In addition, all controls must have used allopurinol at least 6 months without the evidence of any cutaneous reactions. Five studies [10,12-15] also conducted a case control study but used general population as a control group (Table 1). Five studies [10,11,13-15] examined subjects of Asian descent, whereas Lonjou et al [12] examined mixed European population. Hung et al [10] studied Han Chinese population in Taiwan, while Kaniwa et al [11] and Tassaneeyakul et al [13] investigated in Japanese and Thai populations, respectively. In addition, Kang et al [14] and Jung et al [15] studied in Korean population.
All studies determined HLA-B*5801 in cases using PCR-based genotyping and sequence-based typing methods. Since two studies [11,12] used population-controls, there were no descriptions on how genetics of controls were assessed. All studies [11-15] used blood as samples for genotyping, except Hung et al [10] which did not report the source of genetic material. None of the included studies described a blinding procedure for personnel performing genotyping.
Quality assessment
The methodological quality of all studies was shown as mean Newcastle-Ottawa scale of 5 (range from 3 to 7; maximum possible score, 9) (Table 1). Four studies [10,13-15] using matched controls had scores range from 4-7, while the other two studies [11,12] utilizing population controls received lower quality score of 3.
Quantitative synthesis
Four studies with 55 SJS/TEN cases and 678 matched-controls were included in the comparisons of carrier frequency to examine the gene association between cases and allopurinol-tolerant controls [10,13-15]. For these 4 studies, the number of HLA-B*5801 carriers was 54/55 and 74/678 among cases and controls, respectively. Five studies [10-12,14,15] with 69 SJS/TEN cases and 3378 population-controls were included in a separate analysis of carrier frequency to test the association of the HLA-B*5801 genotype and allopurinol induced-SJS/TEN compared to the general population. Cumulative carrier frequency for these three studies was 50/69 for cases and 171/3378 for population-controls, respectively.
Table 3 summarizes the results of all comparisons. All studies demonstrated a statistically significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. In the primary analyses, SJS/TEN cases were significantly more likely to carry HLA-B*5801 allele compared with both matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001) (Figure 2). There was no apparent publication bias as revealed by Begg's and Egger's test (Egger's test for bias, p = 0.732 and Begg's test for bias p = 0.602). No statistically significant heterogeneity was found based on I-squared (I2 = 0.0%) and Q-statistics (p = 0.482 for matched-control and p = 0.751 for population-control).
Table 3. Number of patients who had HLA-B*5801 allele positive and summary odds ratios
Figure 2. Forest plot. A forest plot demonstrating the association between HLA-B*5801 and allopurinol-induced SJS/TEN in matched- and population-control of included studies.
Sensitivity analyses
Subgroup analysis for Asian and non-Asian population cohorts revealed similar findings. Analyses demonstrated a statistically significant association between allopurinol-induced SJS/TEN with the summary odds ratio of 74.18 (95%CI 26.95-204.14) and 101.45 (95% CI 44.98-228.82) for Asian and non-Asian populations, respectively.
Our findings indicate that HLA-B*5801 allele is significantly associated with increased risk of developing SJS/TEN in patients using allopurinol. This severe adverse event associated with allopurinol could be prevented if such genetic information is known a priori. Clinicians and policy makers may use our findings as a foundation to support the implementation of genetic testing prior to initiation of allopurinol.
These findings reveal that the risk of developing SJS/TEN among those allopurinol users with HLA-B*5801 is significantly increased by 80-97 times compared to those without the gene. The sensitivity analyses suggested that the summary odds ratios remained significant regardless of populations. These findings are suggestive of the potential of genotyping in a wide range of population.
Several strengths of our research work deserve more discussion. First, our study is the first one including all kinds of studies determining association of HLA-B*5801 and SJS/TEN development. Second, all SJS/TEN cases were in accordance with the consensus definition [16-18]. These stringent inclusion criteria lowered the risk of misclassification, resulting in increased reliability of our research findings. Third, our meta-analysis adopted the Newcastle-Ottawa scale [19] as a tool to evaluate quality of all case control studies. The Newcastle-Ottawa approach has been reported in several articles to have a good validity for assessing the observational study [25-28]. The average quality score of 5 represented a good quality of overall evidence.
Meta-analysis is not only pooling studies' findings, but this analysis can also determine heterogeneity occurred among the selected studies. The results from our sensitivity analysis demonstrated no significant heterogeneity among populations despite differences in their allele frequency between Asian and non-Asian. Thus, it is justified to perform such analysis despite similarity in the trend of results from the chosen reports. Our findings revealed that despite some differences in several characteristics (e.g. race, sources and selection of control), the association is still consistent and suitable for pooling using meta-analytic technique [29].
Despite the absence of statistical significance of publication bias tests, a possible existence of publication bias cannot be excluded. Because of a relatively small number of total sample size and limited number of studies, the power of publication bias tests might not be sufficient. Even though the meta-analysis shows a consistent significant association of HLA-B*5801 and SJS/TEN in all studies, the overall estimates should be interpreted with caution.
One interesting debate ongoing regarding association between HLA-B*5801 on the risk of developing SJS/TEN is its nature. It has been proposed by Hung et al [10] that HLA-B*5801 was necessary but might not be the only factor related to the risk of SJS/TEN development. Lonjou et al [12] stated that the gene was an important element, but it was neither necessary nor sufficient. All cases in three studies [10,13,15] had HLA-B*5801 allele, whereas the prevalence ranged from 40-80% among cases in the other 3 studies [11,12,14]. The lack of HLA-B*5801 in some cases in the latter 3 studies made it clear that such gene was not the sole factor required. We believe that SJS/TEN development is multifactorial. Other factors including other genes and environment might have a role in the development. What we can conclude was consistent with the summary of Hung et al [10], which was that HLA-B*5801 had a significant role in SJS/TEN occurrence. More research is necessary to further elucidate on how this gene and other factors are involved in allopurinol-induced SJS/TEN pathogenesis.
The increased risk of developing SJS/TEN in those subjects with HLA-B*5801 can be explained by the involvement of cytotoxic T-cells and amplification following cytolytic cytokine. The pathogenesis of drug hypersensitivity is postulated to have direct involvement with human leukocyte antigen (HLA) genes [9,30]. HLA genes located on the major histocompatibility complex (MHC) region of the human chromosome 6p21.3, play a central role in the immune reaction by presenting an antigen to the T cell receptor (TCR) [30].
Despite several postulated mechanisms for the association of HLA-B*5801 and allopurinol-induced SJS/TEN, thus far, there is no definitive proven mechanism. Nonetheless, an immunologic mechanism might play a role in SJS/TEN development [31-33]. Several protein molecules play an important role in this complex process. For instance, MHC proteins, T-cell receptors and some cellular drug metabolizing enzymes (i.e. cytochrome P450 and Phase II metabolizing enzymes) can contribute to the hapten formation and ensuing immunological responses [34]. Although, when the hapten is completely developed and presented at the surface of a nascent T-cell and B-cell clone, they need to proliferate and fully exert their cellular actions. Thus, the fate of these cells can determine the final outcome [35]. These cells may divide and expand resulting in the final immune responses, or get into apoptosis and die out. To elucidate this clonal selection/expansion event among T-cells and B-cells in the SJS/TEN development, a stochastic behavior of the cells is possible [36]. Therefore, a mathematic model describing clonal selection/expansion processes may be useful [37-39]. Nevertheless, this cellular event of the clonal selection/expansion may contribute to the low incidence of SJS/TEN observed in the general population.
Apart from the fate of the nascent antigen specific T- and B-cells, downstream events after binding between the HLA-B*5801 and its receptor may influence the T-cell stimulation. As HLA-B*5801 is presented at the surface, it requires T-cell receptor to couple with the antigen. Subsequently, the immunological system is stimulated [10,30]. The lack of SJS/TEN development might be explained by a malfunction of the T-cell receptor, which could be due to T-cell receptor polymorphism [40,41]. Another putative cause might be an existence of a gene exerting inhibitory effect, resulting in lower risk of SJS/TEN development. In a study of Alfirevic and colleagues [42] investigating the association between genes and SJS/TEN among carbamezepine (CBZ) users, despite small sample size, among those whose possess HLA-B*0702, a significant protective effect for the development of severe reaction was reported. The mechanism of this protective effect is not fully understood.
The association between HLA-B*5801 allele and allopurinol-induced SJS/TEN is consistent across different populations, both Asian and non-Asian [10-15], whereas, an association between HLA-B*1502 and CBZ-induced SJS/TEN demonstrated less consistency [12,43,44]. HLA-B*1502 allele, whose an association with CBZ-induced SJS/TEN is significant in most Asian populations, but not in Japanese and European population. These discrepancies might be explained by the different genetic background. Since this gene is also present in many populations (i.e. African, Caucasian, and Asian), therefore, the association of HLA-B*5801 allele with allopurinol-induced SJS/TEN can be found in various ethnic groups. On the other hand, HLA-B*1502 allele is only present in limited populations (i.e. Asian population) [45].
Interestingly, HLA-B*5801 has a more pronounced effect on allopurinol-induced SJS/TEN compared to those found in the case of HLA-B*1502 and CBZ-induced SJS/TEN. In the latter case, the incidence may be associated with other contributing factors (i.e. other genes) to trigger the adverse drug reaction, whereas those factors may play less role in initiating SJS/TEN in case of HLA-B*580. A study in Japan [46] reported that CBZ-induced SJS/TEN was associated with HLA-B*1511, a member of HLA-B75 type that also includes HLA-B*1502, HLA-B*1508, HLA-B*1515, HLA-B*1521, HLA-B*1530, and HLA-B*1531. These suggested that not only HLA-B*1502 but also other HLA-B75 members are risk factors for CBZ-induced SJS/TEN. By comparison, the strong association between HLA-B*5801 and allopurinol-induced SJS/TEN has been validated in different populations and may be a universal phenomenon since it has been identified in all Chinese, Japanese, Thai, Korean and European patients [10-15].
Notably, a main caveat in this study is the potential misinterpretation of our research findings. This meta-analysis revealed the significant association of HLA-B*5801 allele and the increased risk of allopurinol-induced SJS/TEN. This does not mean that having HLA-B*5801 test done will result in absolutely no risk of allopurinol-induced SJS/TEN. Monitoring of signs and symptoms in these patients are still needed.
Our study is also only limited to the investigation of the association between HLA-B*5801 and allopurinol-induced SJS/TEN. In fact, there has been a number of studies reporting a potential association of DRESS (Drug Rash with Eosinophillia and Systemic Symptoms) and HLA-B*5801 [10,47]. The interpretation of our findings should be limited to SJS/TEN cases and not be generalizable to other severe cutaneous adverse reactions (SCARs).
The implications of our research findings are more likely significant among population with high prevalence of HLA-B*5801. Based on the strong association of the presence of HLA-B*5801 alleles and SJS/TEN, it is presumed that the attributable risk of SJS/TEN due to the existence of this gene is larger among those with the gene. Allele frequency was reported as high as 6-8% among Southeast Asian population and < 1% among Western European population [8,45]. From our results, a genotypic testing of the HLA-B allele may have a benefit to the patients before receiving the drug; particularly in high risk population (e.g. Asian). Knowing the HLA-B allele status of allopurinol users may guide clinicians in determining the optimal choice in order to lower the likelihood of allopurinol-induced SJS/TEN. Presumably these events are avoidable; it might be prudent to consider whether such genetic test should be adopted into routine practice in high-risk population. In order to convince the policy makers to support such genetic testing, a formal cost-effectiveness analysis is warranted.
We found a strong association between HLA-B*5801 allele and allopurinol-induced SJS/TEN in both Asian and non-Asian population. Knowing the HLA-B allele status may be beneficial to some groups of patients who are about to start receiving allopurinol as such information may help clinicians in determining the optimal drug therapy.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
RS, EEE and SS searched and retrieved data, performed the statistical analysis, interpreted results, and drafted the manuscript. ML interpreted results and drafted the manuscript. NC participated in the concept and design of the study, interpreted results, and drafted the manuscript. All authors read, revised and approved the final manuscript.
This study was supported by grants from National Science and Technology Development Agency, Thailand and The Thailand Research Fund (TRF) for The Royal Golden Jubilee PhD Program (Grant No. PHD/0067/2551). The authors would like to thank Associate Professor Dr. Wichittra Tassaneeyakul, Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand for comments and suggestions on the discussion part.
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