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| View Exclusive AAUP Compensation Survey Data |
With many states' economies rebounding, lawmakers are increasing funding for higher education and holding down tuition prices. Are things returning to a pre-recession normal, or simply taking another step toward a new model?
New Jersey's opaque process of divvying up $1.3 billion in state money for capital projects leaves many unhappy with the proposed plans. But few "best practices" exist.
Community colleges struggle to serve a growing share of disadvantaged students, report finds, while public funding skews toward four-year institutions.
As budget crunch eases at California's community colleges, a lawmaker pushes two-tiered tuition, a solution both faculty groups and system leaders oppose.
Use of non-need-based aid in pursuit of tuition revenue and prestige is driving up the cost of college for low-income families, New America Foundation report finds.
Discount rates at private colleges continue to grow, according to annual survey, reflecting the myriad pressures that are weakening college pricing power.
Students at the University of New Mexico, again asked to shoulder a larger financial burden to support athletics, feel their protests are being ignored. Their experience is common.
State lawmakers say the U. of Wisconsin system's budget balances are excessive. Higher education officials say that criticism is a misreading of how university budgets work. It's not the first such conflict, and it won't be the last.
After winning over boards of some small colleges, movement to divest endowments from fossil fuel companies gains momentum. But while pressure is likely to increase, wealthy institutions worry about financial cost.
Report on the fiscal environment for public higher education sees the status quo as unsustainable and urges greater collaboration between college leaders and state policy makers.
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Mineblocks 2
Minecraft For Free Online FanPage
More games
Game info
9555 plays
Date added: 2012-10-19
Description: One of small action Micraft game is Mineblocks 2. Many rivals are attacking into the Minecraft village. A Minecraft boy wants to become a super hero. You must help him wipe out the enemies to protect his village. When you destroy all enemies, you will win the game.
Instructions: Use arrow keys to move your character.
Use C key to jetpack.
Use Space bar to attack.
Use Z key to use the next weapon.
Use Shift key to defend.
Use C key to jetpack.
Use Space bar to attack.
Use Z key to use the next weapon.
Use Shift key to defend.
Tags: mineblocks minecraft action mine blocks
Log-in to add a comment
hobl1630 (1216) - 2013-08-23, 09:001/5
dylan007reed (1061) - 2013-02-27, 12:22BOOO I CANT EVEN EXPLORE THE GAME RIP OFF
Rammy07 (471) - 2013-01-13, 18:18Actully, MineBlocks 2 (the real one) just came out.
creeper123456 (277) - 2012-12-08, 10:28the game is easy
Stealthbomber 19 (2079) - 2012-11-11, 00:59in the description they cant even spell minecraft right they must be complete imbeciles who r trying to make us play so they made a familiar title but with a 2
Stealthbomber 19 (2079) - 2012-11-08, 22:57Its nothing like mineblocks its rubbish thats what it is
victor (497) - 2012-10-28, 02:13howe do i play thias ga,e
bigger1213 (902) - 2012-10-21, 10:01FALSE ADCERISING
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subset: commoncrawl


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Maingate Resort & Spa, Kissimmee
- Free WiFi and free parking
Main amenities
- Restaurant and bar/lounge
- Outdoor pool
- Breakfast available
- Free theme park shuttle
- Business center
- 24-hour front desk
- Coffee/tea in the lobby
- Air conditioning
- Daily housekeeping
- Arcade/game room
- ATM/banking services
- Self-serve laundry
What's around
- Heart of Kissimmee
- Disney's Animal Kingdom® Theme Park (2.7 mi / 4.3 km)
- Disney's Hollywood Studios® (4.7 mi / 7.6 km)
- Walt Disney World® (7.6 mi / 12.2 km)
- Downtown Disney® area (6.9 mi / 11.1 km)
- Epcot® (7.3 mi / 11.8 km)
The room itself was clean and in good condition. My only complaints, half the hotel was…
Very nice hotel, conveniently located near Disney world parks. Hardly takes 5-10 minutes…
Enter dates to check prices
Hotel Info: 866-266-9798from $83 CAD
- Deluxe Room, 2 Queen Beds
- Deluxe Room, 1 King Bed
- Standard Room, 1 King Bed, Non Smoking, Poolside
- Double Room, 2 Double Beds, Non Smoking
- Standard Room, 1 King Bed, Non Smoking
- Standard Room, 1 Queen Bed, Accessible, Non Smoking
- Deluxe Room, 1 King Bed
- Standard Room, 2 Queen Beds
- Suite, 2 Bedrooms, with Loft
- Deluxe Room (Two Queen Beds)
- Double Room, 2 Double Beds, Non Smoking, Poolside
- Deluxe Room, 1 King Bed with Sofabed
- Deluxe Room, 2 Queen Beds
- Standard Room
Recommended hotels
At a glance
Key facts
Hotel size
- This hotel is arranged over 2 floors
- 24-hour check-in
- Check-out time is 11 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
- Minimum check-in age is 21
Travelling with others
- Pets not allowed
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
- Accessible parking
- Free RV/bus/truck parking
- Free theme park shuttle
Nearby Three Star Kissimmee hotels
In the hotel
- Cooked-to-order breakfast daily (surcharge)
- Restaurant
- Bar/lounge
- Coffee/tea in the lobby
- Outdoor pool
- Golfing nearby
- Arcade/game room
- Business center
- 24-hour front desk
- Concierge desk
- Tours/ticket assistance
- Laundry facilities
- ATM/banking
- Designated smoking areas
- Disabled parking
- Accessible path of travel
- Accessible bathroom
- In-room accessibility
In the room
- Climate control
- Air conditioning
- Coffee/tea maker
- Iron/ironing board
- Blackout drapes/curtains
- Premium bedding
- Private bathroom
- Shower/tub combination
- Designer toiletries
- Hair dryer
- 32-inch flat-screen TV
- Premium TV channels
- IPod docking station
- Desk
- Free WiFi
- Free local calls
- Refrigerator
- Daily housekeeping
- In-room safe
- Connecting/adjoining rooms available
- Access via exterior corridors
Top Kissimmee hotels
Recently reviewed hotels in Kissimmee
- Holiday Inn Orlando International AirportFrom
"Enjoyed the hotel but was there only one night. Would stay there again Room neat and clean . Close to highway and only 6 minutes to airport Very close to airport"May 8, 2015
- Hampton Inn & Suites Orlando Airport at Gateway VillageFrom
- Holiday Inn Resort Orlando - Lake Buena VistaFrom
"The only issue we had the wad shower is in a really hard position for my boyfriend who is in a wheel chair, " in the barrier free room". if your sitting on the chair you cant…"May 8, 2015
- Hilton OrlandoFrom
"We got to our Hotel late on a Sunday night and regretted right away not checking in sooner and taking advantage of the Pool area. We spent the next day enjoying the outdoor space…"May 8, 2015
Nearby hotels
Maingate Resort & Spa, Kissimmee's small print
The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation.
Noise-free guestrooms cannot be guaranteed.
This property does not have elevators.
The name on the credit card used at check-in to pay for incidentals must be the primary name on the guestroom reservation.
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


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Will a Democratic Hawaii delegation succeed in a GOP-led Congress?
Hawaii's two Democratic U.S. senators will be in the minority when they head to Washington, D.C. next year. What will that mean for the bill…
Illegal traffic sign points to problems on Kailua roads
While it's still not clear who put up an illegal roadside sign in Kailua, residents tell KHON2 they know the reason it's there.
Voter turnout dismally low, but some counties buck the trend
According to election officials, just 52.3 percent of voters statewide turned out for the election, or 369,554 people.
Hawaii General Election 2014 voter turnout
When looking at voter turnout maps, we pull the data for a specific race that is limited to the area in question. This year, there were no H…
State hospital escapee arrested for shoplifting
A woman who escaped from Hawaii State Hospital two weeks ago is back in custody.
Hawaii County lava flow and eruption videos (Nov. 5)
Videos of the Puna lava flow taken on Nov. 5, 2014.
Police seeking Waipahu Transit Center robbery suspect
The Honolulu Police Department is seeking the public's assistance in identifying a robbery suspect.
Election results show money doesn't guarantee votes
Tuesday's general election results did not always align with the cash-rich committees that backed them, especially on ballot issues.
Vanna White: How she joined 'Wheel' and a surprising hobby
As co-host of the hit game show "Wheel of Fortune", Vanna White has a glamorous job. KHON2's Marisa Yamane gets the inside scoop on how Whit…
Voters approve Maui County GMO ban, now what?
Now that Maui County residents have voted to place a moratorium on genetically modified organisms (GMOs), what does the ban mean and what ca…
You can soon pick your emoji's skin tone
A proposal to expand the skin color options for emojis may get the thumbs up from those calling for more diversity in the icons.
Ask HPD: When to turn on headlights?
Detective Sharie Souza of the Honolulu Police Department Criminal Investigation Division will answer this week's question from a viewer.
Hawaii General Election 2014 detail maps
Note: For statewide races, the polygons may take a little while to render. Click here for precinct detail maps. Click here for voter turnout…
Rep. Gabbard finishes her National Guard duties in Pahoa
U.S. Rep. Tulsi Gabbard assisted in the response to the ongoing Kilauea lava flow.
Iosefa returns to football practice, will play Saturday
The senior runningback served his three-game suspension and pleaded no contest to a DUI charge following an arrest last month.
Hawaii County lava flow and eruption videos (Nov. 4)
Videos of the Puna lava flow taken on Nov. 4, 2014.
Primetime programming changes for Tuesday, Nov. 4
KHON2's regular primetime programming is preempted for KHON2's general election coverage Tuesday night.


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Faith of Our Fathers
"Faith of Our Fathers" doesn't work, and not because of its Christian message. The main problems are the obvious script, the bad acting, and the…
"Faith of Our Fathers" doesn't work, and not because of its Christian message. The main problems are the obvious script, the bad acting, and the…
Schwarzenegger has turned into your elderly uncle, dancing like a goofball at your wedding after a couple glasses of champagne. He knows he's being silly,…
"The Ballad of Narayama" is a Japanese film of great beauty and elegant artifice, telling a story of startling cruelty. What a space it opens…
Patrice Leconte's "Monsieur Hire" is a tragedy about loneliness and erotomania, told about two solitary people who have nothing else in common. It involves a…
Nick Allen picks one of his favorite Roger reviews.
An excerpt of Tony Fitzpatrick's column, "Dime Stories," which has its first published compilation in stores this month.
Nick Allen picks one of his favorite Roger reviews.
An excerpt of Tony Fitzpatrick's column, "Dime Stories," which has its first published compilation in stores this month.
A review of Han Gong-ju from a Far Flung Correspondent.
An FFC responds to Kyle Smith's assertion that women can't enjoy GoodFellas.
The table of contents for RogerEbert.com's complete coverage of AFI Docs 2015.
An interview with "Amy" director Asif Kapadia and producer James Gay-Rees.
Now that we know Quentin Tarantino can make a movie like "Reservoir Dogs," it's time for him to move on and make a better one.
This film, the first from an obviously talented writer-director, is like an exercise in style. He sets up his characters during a funny scene in a coffee shop, and then puts them through a stickup that goes disastrously wrong. Most of the movie deals with its bloody aftermath, as they assemble in a warehouse and bleed and drool on one another.
The movie has one of the best casts you could imagine, led by the legendary old tough guy Lawrence Tierney, who has been in and out of jail both on the screen and in real life. He is incapable of uttering a syllable that sounds inauthentic. Tierney plays Joe Cabot, an experienced criminal who has assembled a team of crooks for a big diamond heist. The key to his plan is that his associates don't know one another, and therefore can't squeal if they're caught. He names them off a color chart: Mr. White, Mr. Orange, Mr. Blonde, Mr. Pink, and so on. Mr. Pink doesn't like his name. "You're lucky you ain't Mr. Yellow," Tierney rasps.
The opening scene features an endlessly circling camera, as the tough guys light cigarettes and drink coffee in one of those places where the tables are Formica and the waitresses write your order on a green-and-white Guest Check. They argue, joke and b.s. each other through thick clouds of smoke; it's like "The Sportswriters on Parole." There's a funny discussion of tipping. Then they walk out of the restaurant, and are introduced in the opening credits, as they walk menacingly toward the camera. They have great faces: The glowering Michael Madsen; the apprehensive Tim Roth; Chris Penn, ready for anything; Tierney, with a Mack truck of a mug; Harvey Keitel, whose presence in a crime movie is like an imprimatur.
The movie feels like it's going to be terrific, but Tarantino's script doesn't have much curiosity about these guys. He has an idea, and trusts the idea to drive the plot.
The idea is that the tough guys, except for Tierney and the deranged Madsen, are mostly bluffers. They are not good at handling themselves in desperate situations.
We see the bungled crime in flashbacks. Tarantino has a confident, kinetic way of shooting action - guys running down the street, gun battles, blood and screams. Then the action centers in the warehouse, where Madsen sadistically toys with a character he thinks is a cop, and the movie ends on a couple of notes of horrifying poetic justice.
One of the discoveries in the movie is Madsen, who has done a lot of acting over the years (he had a good role in "The Natural") but here emerges with the kind of really menacing screen presence only a few actors achieve; he can hold his own with the fearsome Tierney, and reminds me a little of a very mean Robert De Niro.
Tarantino himself is also interesting as an actor; he could play great crazy villains.
As for the movie, I liked what I saw, but I wanted more. I know the story behind the movie - Tarantino promoted the project from scratch, on talent and nerve - and I think it's quite an achievement for a first-timer. It was made on a low budget. But the part that needs work didn't cost money. It's the screenplay. Having created the characters and fashioned the outline, Tarantino doesn't do much with his characters except to let them talk too much, especially when they should be unconscious from shock and loss of blood.
A rebuttal to Joni Edelman's piece on "Inside Out."
This message came to me from a reader named Peter Svensland. He and a fr...
What should be nominated for Emmys this year? Let us guide the way.
An essay on the underrated scores of late composer James Horner.


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DUBAI, United Arab Emirates — The United Arab Emirates on Sunday inaugurated a much-anticipated overland oil pipeline that bypasses the Strait of Hormuz, giving the OPEC member insurance against Iranian threats to block the strategic waterway.
The 236-mile Abu Dhabi Crude Oil Pipeline snakes across western desert dunes and over the craggy Hajar mountains to the city of Fujairah on the UAE's Indian Ocean coast, south of the strait.
Until now, all Emirati exports were loaded in the Gulf and then sailed out through Hormuz. Once it is running at full capacity, the pipeline could allow the country, OPEC's third biggest exporter, to ship as much as two-thirds of its peak production through the eastern port city.
Families spending lesson college, survey shows
CHICAGO — Families have implemented more cost-saving strategies to cut college spending in the past academic year, choosing less expensive schools and finding more economical ways for students to attend.
More students also are living at home in order to help afford college, according to a survey being released Monday by Sallie Mae, the country's largest student lender.
The survey also shows the average amount spent on college by families responding to the survey declined by 5 percent in the 2011-12 school year. More parents and students alike said they make their college decisions based on the cost they can afford to pay than in the previous four studies.
"This really reflects the economic conditions that we see today," said Sarah Ducich, senior vice president at Sallie Mae.
The Ipsos polling firm conducted the study for Sallie Mae based on telephone interviews in April and May with 1,601 college undergraduates and parents.
NY Fed told of interest rate manipulation in '07
The Federal Reserve Bank of New York released documents Friday that show it learned five years ago of big banks understating their borrowing costs to manipulate a key interest rate.
The documents also show Treasury Secretary Timothy F. Geithner, who was then president of the New York Fed, urged the Bank of England to make the rate-setting process more transparent.
A congressional panel requested the documents and is investigating manipulation of the London interbank offered rate (LIBOR), which affects interest people pay on loans.
The process for setting LIBOR has come under scrutiny since Britain's Barclays bank admitted two weeks ago that it had submitted false information to keep the rate low. In settlements with U.S. and British regulators, the bank agreed to pay a $453 million fine.
JPMorgan: Bad trade has ballooned to $5.8B
NEW YORK — JPMorgan Chase said Friday that a bad trade had cost the bank $5.8 billion this year, almost triple its original estimate, and raised the prospect that traders had improperly tried to conceal the blunder.
"This has shaken our company to the core," CEO Jamie Dimon said.
The bank said managers tied to the bad trade had been dismissed without severance pay and that it planned to revoke two years' worth of pay from each of those executives.
JPMorgan said it had lost $4.4 billion because of the trade from April through June, and its chief financial officer said the bank had lost an additional $1.4 billion in the first three months of the year.
• From wire dispatches and staff reports


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Tom Renney on Oilers Lunch now
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Cold North Comrade
Join Date: Jul 2006
Location: Sherwood Park, AB
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Originally Posted by
Actually when Stauffer talked about this more directly the other day. He specifically said certain vets resented that the young guys got the spotlight and it basically angered them that everyone was talking about the young guys leading the team. So Stauffer said they made sure that the rookies were consistently put in their and basically kept down. Maybe I was reading too much into what Stauffer was saying but impression I got was they were being mean to the young guys and treating them like second class citizens.
Tambellini later in last season said the leadership core needed to be changed. He said then maybe the young guys will feel comfortable to take on a larger role with a different leadership core. Which seemed to dove tail a little with what Stauffer seems to be saying.
Couple that with the fact that Moreau in the media blamed the teams problems on the young forwards. Then last year he publicly threw the young goalies under the bus saying we need to score 5,6,7 goals with these young goalies to win a game. You know if he said those things publicly he was probably doing the same or worse in the room. Then recently Moreau basically said that it was being on a bad team and not him playing poorly. Just a couple of examples (among a number of them) that kind of point a finger IMO in Moreau's (not that I think it is all his fault by any means) direction. Stauffer's comments only seem to re-enforce what a lot of people wondered if it was going on.
So I think we are viewing this form a very different point of view. I mean couple all of that above with hints from people like Guy Flaming that Souray may have kind of had it in for his teammate Tom Gilbert. Then add to that Rishaug's comments about Souray being a negative cloud in the locker room and constantly complaining about everything in front of all of the boys.
When I hear stuff like that it makes it harder for me to push the blame on a couple of cocky kids. I do not know for sure of course. But we get different impressions of things.
This sort of thing would explain why the team had considerable difficulties coming together, and why pretty much all the 'captain material' was or is being shipped out ASAP.
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Originally written on The Detroit Sports Site | Last updated 12/11/12
The third-ranked Michigan Wolverines are in line for an NCAA Tournament date at The Palace of Auburn Hills, according to ESPN bracketologist Joe Lunardi. In his first bracket projection of the regular season, Lunardi handed Michigan the No. 1 seed in the West, with Rounds 2 and 3 set for Auburn Hills. You can check out Lunardi's full bracket here. Michigan, presumably, has the fourth No. 1 seed since Lunardi placed the Maize and Blue on the same side of the bracket as Midwest No. 1 Indiana — the brackets are drawn so the highest and lowest No. 1 seeds would play in the Final Four, with the second- and third-rated top seeds in the other semifinal. Lunardi's opponent for Michigan in Round 2 (remember, "Round 1″ is not the four-game play-in): Canisius, of the MAAC. The next foe in this hypothetical would be either No. 8 seed Butler or No. 9 Cal. Despite a little bit of a rocky start to 2012-13, Michigan State also claimed a fairly cushy spot in Lunardi's bracket: The Spartans are a No. 5 seed in the East, with a Round 2 matchup in San Jose against Colorado State. No. 4 seed Gonzaga and No. 13 Florida Gulf Coast are penciled in as the other matchup in that sub-regional. All told, Lunardi handed out seven spots to Big Ten teams, tying it with the Big East and ACC for most bids from one conference.
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Divine Chocolate Bar - 1.5 oz
Roll over image to zoom in
As seen on Oprah!
One word: Chocolate.
A gourmet delight that lives up to its name, Divine Chocolate is made with only the finest quality, fairly traded cocoa beans from Kuapa Kokoo, a cooperative of smallholder farmers in Ghana. The cocoa is grown in the shade of the tropical rainforest,and slowly fermented and dried in the sun by farmers who take great pride in the chocolate company they co-own. Choosing delicious Divine gives you guaranteed pleasure -- and the farmers a guaranteed fair deal and chance to invest in a better future.
- Dark Chocolate ingredients: cocoa mass (70% cocoa solids), sugar, cocoa butter, emulsifier: soya lecithin (non GM), vanilla
- Milk Chocolate ingredients: sugar, cocoa butter, dried cream, cocoa mass, whole milk powder, emulsifier: soya lecithin(nonGM), vanilla
- Toffee Crunch ingredients: sugar, cocoa butter, dried cream, toffee, glucose syrup, butterfat, salt, emulsifier: soya lecithin (non GM), vanilla
- Fair Trade Certified
- Net wt. 1.5 oz
- Handmade and fairly traded from Ghana
May contain trace amounts of nuts and wheat.
Created to help women worldwide gain economic security for themselves and their families by earning fair wages for their handiwork, Global Girlfriend sources women-made, fair-trade imported, eco-friendly products. By supporting long-term partnerships with the artisans, it fosters equal employment opportunities, healthy and safe working conditions, technical assistance, and development strategies to help reduce poverty, one community at a time. Become a "Global Girlfriend" and help build a brighter future for girlfriends around the globe!
For bulk pricing on these and other items, please contact our Customer Service department at email@example.com.
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May 7, 2015 - This is really good chocolate. The only thing I am upset about is that I didn't add more to my last order! I will definitely be stocking up on my next order and trying other kinds, too, as I have only bought the Dark each time I have purchased. Great as gifts, if they can last that long to give away:)
February 28, 2015 - This is one of the best milk chocolate bars i have ever eaten!!!!! And i have had two of these beauty's!
February 11, 2015 - Great taste!
February 2, 2015 - This is one of the best chocolates I've ever eaten--creamy and delicious! I will buy again and again. Not only do I get to indulge my passion for chocolate, but I also get to help out other human beings. Thank you for providing this and the other sites.
November 30, 2014 - Delicious, creamy chocolate. This bar was gone in seconds!
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Debbie Gibson, Darrell Hammond to Judge New ABC Series SING YOUR FACE OFF, 5/31
|Related Links
|AsOne Hits #1 on Billboard Chart With Self-Titled Debut Inspirational Album
July 02, 2015
|Related: SING YOUR FACE OFF, ABC, Reality TV
ABC's "SING YOUR FACE OFF" will premiere on May 31, featuring host John Barrowman and primary judges Debbie Gibson and Darrell Hammond.
"Sing Your Face Off," a talent variety competition featuring celebrities who are transformed and trained to perform as legendary musical icons, will premiere on SATURDAY, MAY 31 (9:00-11:00 p.m., ET/PT). Over the course of the series, the 5 celebrities (Sebastian Bach/legendary rock star from the band Skid Row; Landry Fields/NBA's Toronto Raptors; Jon Lovitz/comedian, actor, singer; China Anne McClain/Disney Channel's "How to Build a Better Boy" which premieres this summer, "A.N.T. Farm;" Lisa Rinna/"Days of Our Lives") will each take on the identity of a different and iconic music performer -- the celebrities could find themselves transformed into someone far older, younger or even someone of the opposite sex.
From the hours in the makeup chair to the days spent with choreographers and vocal coaches, each show will feature the complete transformation - not just physical - the celebrities will embody everything about the assigned icon - their walk, their talk, and their distinguishing mannerisms leading up to the live performance in front of the studio audience. Viewers will get the chance to see each of the celebrities portray multiple musical performers during the series.
"101" "102"
Sebastian Bach = Adam Levine Sebastian Bach = Lady Gaga
Landry Fields = Lionel Richie Landry Fields = Pitbull
Jon Lovitz = Elton John Jon Lovitz = Pavarotti
China Anne McClain = Rihanna China Anne McClain = Tina Turner
Lisa Rinna = Dolly Parton Lisa Rinna = Britney Spears
John Barrowman ("Arrow," "Torchwood") is the host. Debbie Gibson and Darrell Hammond are the primary judges, while David Allen Grier is the guest judge for "101" and RuPaul Charles is the guest judge for "102."
Based on Endemol's global hit "Your Face Sounds Familiar," "Sing Your Face Off" is produced by Endemol USA. Georgie Hurford-Jones ("America's Got Talent," "Britain's Got Talent") is Executive Producer.
For more information on "Sing Your Face Off," visit ABC.com
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- CNBC to Air THE MAKING OF DIG, the USA Network Event Series, 3/1
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Publications (18)112.24 Total impact
Article: Long-term Dantrolene Treatment Reduced Intraneuronal Amyloid in Aged Alzheimer Triple Transgenic Mice[Show abstract] [Hide abstract]
ABSTRACT: In this study, we investigated the long-term treatment of dantrolene on amyloid and tau neuropathology, brain volume, and cognitive function in aged triple transgenic Alzheimer (3xTg-AD) mice. Fifteen-month old 3xTg-AD mice and wild-type controls were treated with oral dantrolene (5 mg/kg) or vehicle control twice a week for 6 months. Learning and memory were examined using the Morris Water Maze at 21 and 22 months of age. After the behavioral testing, hippocampal and cortical brain volumes were calculated with magnetic resonance imaging and motor function was evaluated using the rotorod. The amyloid burden and tau neurofibrillary tangles in the hippocampus were determined using immunohistochemistry. We found that dantrolene significantly decreased the intraneuronal amyloid accumulation by as much as 76% compared with its corresponding vehicle control, together with a trend to reduce phosphorylated tau in the hippocampus. No significant differences could be detected in hippocampal or cortical brain volume, motor function or cognition among all experimental groups, indicating that the mice were still presymptomatic for Alzheimer disease. Thus, presymptomatic and long-term dantrolene treatment significantly decreased the intraneuronal amyloid burden in aged 3xTg-AD mice before significant changes in brain volume, or cognition.Alzheimer Disease and Associated Disorders 02/2015; DOI:10.1097/WAD.0000000000000075 · 2.69 Impact Factor
Article: Anesthetic Preconditioning Inhibits Isoflurane-Mediated Apoptosis in the Developing Rat Brain[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: We hypothesized that preconditioning (PC) with a short exposure to isoflurane (ISO) would reduce neurodegeneration induced by prolonged exposure to ISO in neonatal rats, as previously shown in neuronal cell culture. METHODS: We randomly divided 7-day-old Sprague-Dawley rats into 3 groups: control, 1.5% ISO, and PC + 1.5% ISO. The control group was exposed to carrier gas (30% oxygen balanced in nitrogen) for 30 minutes and then to carrier gas again for 6 hours the following day. The 1.5% ISO group was exposed to carrier gas for 30 minutes and then to 1.5% ISO for 6 hours the following day. The PC + 1.5% ISO group was preconditioned with a 30-minute 1.5% ISO exposure and then exposed to 1.5% ISO for 6 hours the following day. Blood and brain samples were collected 2 hours after the exposures for determination of neurodegenerative biomarkers, including caspase-3, S100 beta, caspase-12, and an autophagy biomarker Beclin-1. RESULTS: Prolonged exposure to ISO significantly increased cleaved caspase-3 expression in the cerebral cortex of 7-day-old rats compared with the group preconditioned with ISO and the controls using Western blot assays. However, significant differences were not detected for other markers of neuronal injury. CONCLUSIONS: The ISO-mediated increase in cleaved caspase-3 in the postnatal day 7 rat brain is ameliorated by PC with a brief anesthetic exposure, and differences were not detected in other markers of neuronal injury.Anesthesia & Analgesia 08/2014; 119(4). DOI:10.1213/ANE.0000000000000380 · 3.42 Impact Factor
Article: Comparison of Neurodegeneration and Cognitive Impairment in Neonatal Mice Exposed to Propofol or Isoflurane[Show abstract] [Hide abstract]
ABSTRACT: Background While previous studies have demonstrated neuronal apoptosis and associated cognitive impairment after isoflurane or propofol exposure in neonatal rodents, the effects of these two anesthetics have not been directly compared. Here, we compare and contrast the effectiveness of isoflurane and propofol to cause neurodegeneration in the developing brain and associated cognitive dysfunction. Methods Seven-day-old mice were used. Mice in the isoflurane treatment group received 6 h of 1.5% isoflurane, while mice in propofol treatment group received one peritoneal injection (150 mg/kg), which produced persistent anesthesia with loss of righting for at least 6 h. Mice in control groups received carrying gas or a peritoneal injection of vehicle (intralipid). At 6 h after anesthetic treatment, a subset of each group was sacrificed and examined for evidence of neurodegeneration, using plasma levels of S100β, and apoptosis using caspase-3 immunohistochemistry in the cerebral cortex and hippocampus and Western blot assays of the cortex. In addition, biomarkers for inflammation (interleukin-1, interleukin-6, and tumor necrosis factor alpha) were examined with Western blot analyses of the cortex. In another subset of mice, learning and memory were assessed 32 days after the anesthetic exposures using the Morris water maze. Results Isoflurane significantly increased plasma S100β levels compared to controls and propofol. Both isoflurane and propofol significantly increased caspase-3 levels in the cortex and hippocampus, though isoflurane was significantly more potent than propofol. However, there were no significant differences in the inflammatory biomarkers in the cortex or in subsequent learning and memory between the experimental groups. Conclusion Both isoflurane and propofol caused significant apoptosis in the mouse developing brain, with isoflurane being more potent. Isoflurane significantly increased levels of the plasma neurodegenerative biomarker, S100β. However, these neurodegenerative effects of isoflurane and propofol in the developing brain were not associated with effects on inflammation or with cognitive dysfunction in later life.PLoS ONE 06/2014; 9(6):e99171. DOI:10.1371/journal.pone.0099171 · 3.53 Impact Factor
Article: Dual Effects of Isoflurane on Proliferation, Differentiation, and Survival in Human Neuroprogenitor Cells[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND:: Previous studies have demonstrated that isoflurane can provide both neuroprotection and neurotoxicity in various tissue culture models and in rodent developing brains. The cellular and molecular mechanisms mediating these dual effects are not clear, but the exposure level and duration of isoflurane appear to be determinant factors. METHODS:: Using the ReNcell CX (Millipore, Billerica, MA) human neural progenitor cell line, the authors investigated the impact of prolonged exposure to varying isoflurane concentrations on cell survival and neurogenesis. In addition, the authors assessed the impact of short isoflurane preconditioning on elevation of cytosolic Ca concentration and cytotoxic effects mediated by prolonged isoflurane exposures and the contribution of inositol-1,4,5-trisphosphate or ryanodine receptor activation to these processes. RESULTS:: Short exposures to low isoflurane concentrations promote proliferation and differentiation of ReNcell CX cells, with no cell damage. However, prolonged exposures to high isoflurane concentrations induced significant ReNcell CX cell damage and inhibited cell proliferation. These prolonged exposures suppressed neuronal cell fate and promoted glial cell fate. Preconditioning of ReNcell CX cultures with short exposures to low concentrations of isoflurane ameliorated the effects of prolonged exposures to isoflurane. Pretreatment of ReNcell cultures with inositol-1,4,5-trisphosphate or ryanodine receptor antagonists mostly prevented isoflurane-mediated effects on survival, proliferation, and differentiation. Finally, isoflurane-preconditioned cultures showed significantly less isoflurane-evoked changes in calcium concentration. CONCLUSION:: The commonly used general anesthetic isoflurane exerts dual effects on neuronal stem cell survival, proliferation, and differentiation, which may be attributed to differential regulation of calcium release through activation of endoplasmic reticulum localized inositol-1,4,5-trisphosphate and/or ryanodine receptors.Anesthesiology 01/2013; 118(3). DOI:10.1097/ALN.0b013e3182833fae · 6.17 Impact Factor
Article: Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice[Show abstract] [Hide abstract]
ABSTRACT: Disruption of intracellular calcium homeostasis via abnormal and excessive activation of ryanodine receptors plays an important role in the neuropathology of Alzheimer's disease. We investigated the therapeutic effect of dantrolene, a ryanodine receptor antagonist, on cognitive dysfunction and neuropathology in the triple transgenic Alzheimer mouse model (3xTg-AD). 3xTg-AD mice were treated with dantrolene from 2 to 13 months of age. Learning and memory were measured with the Morris Water Maze at 6, 10, and 13 months of age. Amyloid and tau neuropathology and biomarkers for synaptic dysfunction and neurodegeneration were examined in the brain using immunoblotting or immunohistochemistry. Dantrolene treatment for 11 months significantly reduced both memory deficits and amyloid plaque load in the hippocampus in 13-month-old 3xTg-AD mice. Dantrolene treatment, however, had no effect on phosphorylated tau, phosphorylated or total GSK-3β, synaptic markers, or mitochondrial or cytosolic cytochrome C. Our results suggest that dantrolene significantly improves cognition in a murine model of Alzheimer's disease and is associated with a reduction in amyloid plaque burden, forming the basis for a novel therapeutic approach for Alzheimer's disease.Neuroscience Letters 04/2012; 516(2):274-9. DOI:10.1016/j.neulet.2012.04.008 · 2.06 Impact Factor
Article: Early and chronic treatment with dantrolene blocked later learning and memory deficits in older Alzheimer's triple transgenic miceAlzheimer's and Dementia 07/2011; 7(4). DOI:10.1016/j.jalz.2011.09.141 · 17.47 Impact Factor
Article: General anesthetics influence autophagy and neurodegeneration through actions on the inositol 1,4,5-Trisphosphate receptor calcium channelAlzheimer's and Dementia 07/2011; 7(4). DOI:10.1016/j.jalz.2011.05.1618 · 17.47 Impact Factor
Article: The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease[Show abstract] [Hide abstract]
ABSTRACT: Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh(Q111/Q111)) and wild type (STHdh(Q7/Q7)) striatal neurons. The primary cultured neurons were exposed for 24h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP(3)) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh(Q111/Q111) cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh(Q111/Q111) huntingtin cells than in the wild type STHdh(Q7/Q7) striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh(Q111/Q111) cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP(3) receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh(Q111/Q111) striatal cells.Toxicology and Applied Pharmacology 11/2010; 250(3):291-8. DOI:10.1016/j.taap.2010.10.032 · 3.63 Impact Factor
Article: Effects of commonly used inhalational anesthetic isoflurane on intracellular calcium homeostasis and neuropathology in Alzheimer's diseaseAlzheimer's and Dementia 07/2010; 6(4). DOI:10.1016/j.jalz.2010.05.1323 · 17.47 Impact Factor
Article: Isoflurane Causes Greater Neurodegeneration Than an Equivalent Exposure of Sevoflurane in the Developing Brain of Neonatal Mice[Show abstract] [Hide abstract]
ABSTRACT: We hypothesized that isoflurane has a greater potency to induce neurodegeneration than sevoflurane in the developing brains of neonatal mice based on our previous studies in cell culture. We treated 7-day-old mice with either 0.75% isoflurane or 1.1% sevoflurane ( approximately 0.5 minimum alveolar concentration) for 6 h and then obtained blood and brain samples at 2 h after the anesthesia treatment for determination of neuroapoptosis in different brain regions and the neurodegenerative biomarker S100beta in the blood. The mechanisms of neurodegeneration induced by isoflurane or sevoflurane were also compared by determining protein expressions of the cell cycle and apoptosis-related proteins. In separate groups, memory and learning ability were evaluated through the use of Morris Water Maze testing in mice at postnatal day 42 after anesthesia treatment at postnatal day 7. Isoflurane but not sevoflurane significantly increased the neurodegenerative biomarker S100beta in the blood. Isoflurane treatments significantly increased apoptosis indicated by the activation of caspase-3 and elevation of poly-(ADP-ribose) polymerase in different brain regions. An equipotent exposure of sevoflurane tended to increase apoptosis in hippocampal and cortex areas but was significantly less potent than isoflurane. Neither isoflurane nor sevoflurane significantly changed protein levels of glyceraldehyde-3-phosphate dehydrogenase, beta-site amyloid beta-precursor protein-cleaving enzyme, and cell cycle regulatory proteins (CDK4, cyclin D1). Isoflurane and sevoflurane at the selected exposures did not significantly alter memory and learning ability. At equipotent exposures, isoflurane has a greater potency than sevoflurane to cause neurodegeneration in the developing brains of neonatal mice.Anesthesiology 06/2010; 112(6):1325-34. DOI:10.1097/ALN.0b013e3181d94da5 · 6.17 Impact Factor
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ABSTRACT: The commonly used general anesthetic isoflurane induces widespread neurodegeneration in the developing mammalian brain through poorly understood mechanisms. We have investigated whether excessive Ca2+ release from the endoplasmic reticulum via overactivation of inositol 1,4,5-trisphosphate receptors (InsP3Rs) is a contributing factor in such neurodegeneration in rodent primary cultured neurons and developing rat brain. We also investigated the correlation between isoflurane exposure and cognitive decline in rats at 1 month of age. Our results show that isoflurane increases cytosolic calcium in the primary cortical neurons through release from the endoplasmic reticulum and influx from the extracellular space. Pharmacological inhibition of InsP3R activity and knockdown of its expression nearly abolishes the isoflurane-mediated elevation of the cytosolic calcium concentration and cell death in rodent primary cortical and hippocampal neurons. Inhibition of InsP3R activity by its antagonist xestospongin C significantly inhibits neurodegeneration induced by isoflurane at clinically used concentration in the developing brain of postnatal day 7 rats. Moreover, our results show that isoflurane activates beta-site amyloid beta precursor protein-cleaving enzyme via activation of the InsP3R. We also noted that mice exposed to isoflurane during early postnatal development showed transient memory and learning impairments, which did not correlate well with the noted neuropathological defects. Taken together, our results suggest that Ca2+ dysregulation through overactivation of the InsP3R may be a contributing factor in the mechanism of isoflurane-induced neurodegeneration in rodent neuronal cell culture and during brain development.Journal of Pharmacology and Experimental Therapeutics 04/2010; 333(1):14-22. DOI:10.1124/jpet.109.161562 · 3.86 Impact Factor
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ABSTRACT: We investigated the extent of isoflurane-induced neurodegeneration on the fetuses of pregnant rats exposed in utero. Pregnant rats at gestational d 21 were divided into three experimental groups. Rats in the control group spontaneously breathed 100% oxygen for 1 h. Rats in the treatment groups breathed either 1.3 or 3% isoflurane in 100% oxygen through an endotracheal tube, with mechanical ventilation for 1 h. Rat pups were delivered by cesarian section 6 h after treatment, and fetal blood was sampled from the left ventricle of each fetal heart and evaluated for S100beta. Fetal brains were then evaluated for apoptosis, using caspase-3 immunohistochemistry in the CA1 region of the hippocampus and the retrosplenial cortex (RS). The 3% isoflurane treatment group showed significantly higher levels of S100beta levels and significantly increased average densities of total caspase-3-positive cells in the CA1 hippocampus and RS cortex compared with the control and the 1.3% isoflurane groups. There were no differences in S100beta levels or densities of caspase-3-positive cells between the control and 1.3% isoflurane groups. Isoflurane at a concentration of 3% for 1 h increased neurodegeneration in the hippocampal CA1 area and the retrosplenial cortex in the developing brain of fetal rats.Pediatric Research 10/2009; 66(4):435-40. DOI:10.1203/PDR.0b013e3181b3381b · 2.84 Impact Factor
Article: Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies.[Show abstract] [Hide abstract]
ABSTRACT: The authors hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane having greater potency than sevoflurane or desflurane. The authors treated DT40 chicken B lymphocytes with total IP3 receptor knockout or their corresponding wild-type control cells with equipotent exposure to isoflurane, sevoflurane, and desflurane. The authors then determined the degree of cell damage by counting the percentage of annexin V- or propidium iodide-positively stained cells or measuring caspase-3 activity. They also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol, and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane, and desflurane in both types of DT40 cells. Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 h) induced significant cell damage only in DT40 wild-type and not in IP3 receptor total knockout cells, but with significantly less potency than isoflurane. In accord, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied by a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild-type and not in IP3 receptor total knockout cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane. Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.Anesthesiology 08/2008; 109(2):243-50. DOI:10.1097/ALN.0b013e31817f5c47 · 6.17 Impact Factor
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ABSTRACT: Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma neurosecretory cells (PC12) in a concentration- and time-dependent manner via an as yet unknown mechanism. We hypothesize that isoflurane induces apoptosis by causing abnormal calcium release from the endoplasmic reticulum (ER) via activation of inositol 1,4,5-trisphosphate (IP3) receptors. A presenilin-1 (PS1) mutation associated with familial Alzheimer's disease was shown to increase the activity of IP3 receptors, and therefore may render cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane have less ability to disrupt intracellular calcium homeostasis; and thus we predict they will cause less cytotoxicity. PC12 cells transfected with wild type, vector alone (Vector) or mutated PS1 (L286V) were treated with equivalent of 1 MAC of isoflurane, sevoflurane, and desflurane for 12 h. Mitochondria redox activity (MTT reduction) and lactate dehydrogenase release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space ([Ca2+]c) and production of reactive oxygen species (ROS) were determined after exposing different types of cells to various inhaled anesthetics. We also determined the effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells, and in rat primary cortical neurons. Isoflurane at 1 MAC for 12 h induced cytotoxicity in L286V but not wild type or vector PC12 cells, and also caused greater and faster increase of peak [Ca2+]c in the L286V cells. Xestospongin C significantly attenuated isoflurane cytotoxicity in both L286V cells and primary cortical neurons and inhibited the calcium release from the ER in L286V cells. Isoflurane did not induce significant changes of ROS production in any type of PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or increase of peak [Ca2+]c in L286V PC12 cells. Our results show that the L286V PS1 mutation augments the isoflurane-induced [Ca2+]c increase via calcium release from intracellular stores which, in turn, renders the cells vulnerable to isoflurane neurotoxicity. ROS production was not involved in isoflurane-induced neurotoxicity. Sevoflurane and desflurane, at equivalent exposure to isoflurane, did not induce a similar increase of [Ca2+]c or neurotoxicity in L286V PC12 cells.Anesthesia and analgesia 03/2008; 106(2):492-500, table of contents. DOI:10.1213/ane.0b013e3181605b71 · 3.42 Impact Factor
Article: The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors.[Show abstract] [Hide abstract]
ABSTRACT: Isoflurane induces cell apoptosis by an unknown mechanism. The authors hypothesized that isoflurane activates inositol 1,4,5-trisphosphate (IP3) receptors on the endoplasmic reticulum (ER) membrane, causing excessive calcium release, triggering apoptosis. The authors determined isoflurane-induced cytotoxicity by measuring caspase-3 activity, lactate dehydrogenase release, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) reduction, and imaging analysis of cell damage markers (annexin V and propidium iodide staining) in different cell types. The authors used the chicken B lymphocyte with a total knock-out of IP3 receptors, PC12 cells with elevated IP3 receptor activity (transfected with L286V presenilin 1), striatal cells with a knock-in of Q111 Huntingtin, and each cell line's corresponding wild-type controls. The authors also measured the isoflurane-evoked changes of calcium concentration in cytosol and/or mitochondria in these cells. Isoflurane induced apoptosis concentration- and time-dependently, and sequentially elevated cytosolic and then mitochondrial calcium in the chicken B-lymphocyte wild-type but not the IP3 receptor total knock-out cells. Thapsigargin, a calcium adenosine triphosphatase inhibitor on ER membranes, induced apoptosis and elevations of calcium in cytosol and mitochondria in both chicken B-lymphocyte wild-type and IP3 receptor total knock-out cells. Isoflurane induced significantly more neurotoxicity and greater calcium release from the ER in L286V PC12 and Q111 Huntingtin striatal cells than in their corresponding wild-type controls, both of which were significantly inhibited by the IP3 receptor antagonist xestospongin C. These findings suggest that isoflurane activates the ER membrane IP3 receptor, producing excessive calcium release and triggering apoptosis. Neurons with enhanced IP3 receptor activity, as in certain cases of familial Alzheimer or Huntington disease, may be especially vulnerable to isoflurane cytotoxicity.Anesthesiology 03/2008; 108(2):251-60. DOI:10.1097/01.anes.0000299435.59242.0e · 6.17 Impact Factor
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ABSTRACT: In a maternal fetal rat model, we investigated the behavioral and neurotoxic effects of fetal exposure to isoflurane. Pregnant rats at gestational day 21 were anesthetized with 1.3% isoflurane for 6h. Apoptosis was quantified in the hippocampus and cortex at 2 and 18h after exposure in the fetal brain and in the postnatal day 5 (P5) pup brain. Spatial memory and learning of the fetal exposed pups were examined with the Morris Water Maze at juvenile and adult ages. Rat fetal exposure to isoflurane at pregnancy day 21 through maternal anesthesia significantly decreased spontaneous apoptosis in the hippocampal CA1 region and in the retrosplenial cortex at 2h after exposure, but not at 18h or at P5. Fetal exposure to isoflurane did not impair subsequent juvenile or adult postnatal spatial reference memory and learning and, in fact, improved spatial memory in the juvenile rat. These results show that isoflurane exposure during late pregnancy is not neurotoxic to the fetal brain and does not impair memory and learning in the juvenile or adult rat.Neuropharmacology 01/2008; 53(8):942-50. DOI:10.1016/j.neuropharm.2007.09.005 · 4.82 Impact Factor
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ABSTRACT: The commonly used inhaled anesthetic isoflurane has been shown to be both neuroprotective and neurotoxic in various cell cultures and animal models. We hypothesize that, like cerebral ischemia, isoflurane is inherently neurotoxic. Limited exposure of isoflurane provides neuroprotection via induction of endogenous neuroprotective mechanisms (preconditioning), while prolonged exposure of isoflurane induces neurotoxicity directly by its inherent neurotoxic effects. To test this hypothesis, we treated rat primary cortical neurons at different days in vitro (DIV) and rat pheochromocytoma neurosecretory (PC12) cells with or without Alzheimer's mutated presenilin-1 (PS1) with 2.4% isoflurane for 24 h to induce cell damage determined by both MTT (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) reduction and LDH (lactate dehydrogenase) release assays. For isoflurane preconditioning, we treated the above cells with isoflurane at 0.6%, 1.2% and 2.4% for 60 min, 4 h prior to a prolonged exposure of 2.4% isoflurane for 24 h. One hour of preconditioning with isoflurane dose-dependently inhibited neurotoxicity induced by 2.4% isoflurane for 24 h in both primary cortical neurons and PC12 cells. This neuroprotection was most dramatically observed in matured cortical neurons (DIV 16) and PC12 cells with over expression of Alzheimer's mutated PS1 (L286V). Preconditioning L286V PC12 cells with equivalent two minimal alveolar concentrations (MAC) of halothane (1.5%), but not sevoflurane (4%), also abolished the neurotoxicity induced by 2.4% isoflurane for 24 h. Overall, these results suggest that isoflurane may be both neuroprotective and neurotoxic, depending on the exposure concentrations and duration.Neuroscience Letters 10/2007; 425(1):59-62. DOI:10.1016/j.neulet.2007.08.011 · 2.06 Impact Factor
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ABSTRACT: Depletion of calcium from the neuronal endoplasmic reticulum (ER) induces apoptosis. Isoflurane depletes calcium from sarcoplasmic reticulum (SR) of muscle, an analogue of ER in neurons, while sevoflurane maintains or increases SR calcium. We hypothesized that isoflurane, but not sevoflurane, induces apoptosis by depleting the ER calcium. Rat PC12 pheochromocytoma cells and primary cortical neurons were treated with equipotent doses of isoflurane and sevoflurane. Isoflurane, but not sevoflurane, at equipotent doses induced cell damage determined by both LDH release and MTT reduction assays, dose and time dependently, in both types of cells. Isoflurane at 2.4% for 24 h induced cytotoxicity in both cell types, which was characterized by nuclear condensation and fragmentation and activation of caspases 3 and 9. Isoflurane cytotoxicity was suppressed by dantrolene, a ryanodine receptor antagonist that inhibits abnormal calcium release from the ER. Isoflurane decreased the Bcl-2/Bax ratio by as much as 36% (P < 0.05). However, sevoflurane did not cause neuronal damage by apoptosis nor did it decrease the Bcl-2/Bax ratio. These results suggest that isoflurane and sevoflurane differentially affect the Bcl-2/Bax ratio and cell survival. At equipotent concentrations, isoflurane, but not sevoflurane, induces cytotoxicity in both PC12 cells and primary cortical neurons and decreases the Bcl-2/Bax ratio.Brain Research 03/2005; 1037(1-2):139-47. DOI:10.1016/j.brainres.2005.01.009 · 2.83 Impact Factor
Top Journals
- Anesthesiology (4)
- Alzheimer's and Dementia (3)
- Anesthesia & Analgesia (1)
- Brain Research (1)
- Neuropharmacology (1)
William Penn UniversityFiladelfia, Pennsylvania, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
- Department of Anesthesiology and Critical Care
Tongji HospitalWu-han-shih, Hubei, China


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Articles tagged trans fat solution
26 Apr 2010 // 10:00 PM
Food writer Kim Severson's latest is Spoon Fed: How Eight Cooks Saved My Life. Her ideal guests at the Ritz, she tells PopMatters 20 Questions, would be Gertrude Stein, Eleanor Roosevelt and Lucille Ball.READ more
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Colette Carr "Static" (video) (Premiere) // Music
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"PopMatters is on a short summer publishing break. We resume Monday, July 6th.READ the article


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March 10, 2014 - Industry News
The online logistics provider uShip has announced a partnership with the online auction business eBay, when it comes to arranging larger-than-parcel shipments.
Tags: eBay, eBay Motors, uShip, Logistics
We offer e-newsletters that deliver targeted news and information for the entire fleet industry.
The expert, Mark Betner from CITGO, will answer your questions
The expert, Rence Oliphant from Hendrickson, will answer your questions
VentAiRator Vented Visors
J.J. Keller Develops DOT Handbook for Drivers
DTech Adds Two Diesel Fuel Additives
Garmin Navigator Has Built-In Dash Cam


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In an anecdote that will likely be recounted ad nauseam during Jolie-Pitt holidays at the family's French chateau for years to come, one of the actors' six children was reportedly less than enthused by the chance to appear in her mother's latest starring vehicle, Maleficent. Earlier this summer, Disney confirmed that Angelina Jolie and Brad Pitt's four-year-old daughter, Vivienne, would appear in the live-action film, a retelling of Sleeping Beauty from the point of view of the wicked fairy, played by Jolie. (Vivienne will portray the child version of Elle Fanning's Princess Aurora, whom Malificent curses.) In addition, according to a damning new Us Weekly report, Pax (aged eight), Zahara (aged seven), and Shiloh (aged six) were added to the call sheet . . . but one of the three won't make it into the final film.
A source who is not above leaking information about six-year-old children confides in Us Weekly, "Shiloh was supposed to be in [the movie], too, but she was bored and not in the mood during the day her part was supposed to happen, so she ended up not being in the film." This would not have been her first time in front of the camera, however. Shiloh "Can Take It or Leave It" Jolie-Pitt had a brief cameo in her father's The Curious Case of Benjamin Button and, according to her IMDb page, played herself on an episode of VH1: All Access. Maleficent is slated to open in theaters in March 2014.
For more high-profile interviews, stunning photography, and thought-provoking features, subscribe now to Vanity Fair magazine.


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Tuesday, June 9, 2015 at 5 pm - Tom Veneklasen Studio 129 N. Warren. All ASMP Tucson members are welcome to attend
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This is our social event to share work and ideas with fellow members.This one will highlight new members Catrina & Derrick Briscoe


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Orange for Animal Cruelty Awareness wants to
STOP the cruelty of Greyhound Racing
Greyhound Racing kills!
Greyhound Racing kills!
An innocent family dog was brutally tortured over a break up. We must not forget Moon's pain and fight for her justice.
The world is already over populated with innocent animals...why breed more.
Several petitions demanding the END of whale & dolphin hunts in Taiji Japan. Host nation of the Tokyo 2020 Olympics.
Join Fin Free™ & Support the Fin Free Global Movement to Ban Shark Fin Products Worldwide & Save Sharks. Join #finfree!
Endangered species protections for gray wolves and other wildlife are under attack! We need you to act now!


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HOME CBS Kentucky Wildcats Gear Kentucky Wildcats T-Shirts College Basketball Gear (136 items) Product ID: 1605395
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Glen Ellyn Child Care
Choose from 231 child care providers. Average child care costs in Glen Ellyn: $10.75/hr. Share this rate with friends.
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Pronunciation: Lucha
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Prescott finds reported sex offenses lower in neighborhoods with resident sex offenders
Geronimus says poor Detroiters face greater health risks given adverse social conditions
Armstrong's research shows parental advice helps lower risk of campus sexual assaults
Bob Willis awarded 2015 Jacob Mincer Award for Lifetime Contributions to the Field of Labor Economics
David Lam is new director of Institute for Social Research
Elizabeth Bruch wins Robert Merton Prize for paper in analytic sociology
Elizabeth Bruch wins ASA award for paper in mathematical sociology
PSC Brown Bags will be back fall 2015
Cichello, P.L., G.S. Fields, and Murray Leibbrandt. 2005. "Earnings and employment dynamics for Africans in post-apartheid South Africa: A panel study of KwaZulu-Natal." Journal of African Economies, 14(2): 143-190.
The labour market is central in determining individual and household wellbeing in South Africa. Therefore, an understanding of earnings and employment dynamics is a key policy issue. However, the absence of panel data has constrained empirical work addressing these issues. This paper makes use of a regional panel data set for KwaZulu-Natal to begin the study of earnings and employment dynamics. The authors find that, on average, working-aged Africans in KwaZulu-Natal experienced large gains in earnings during the period 1993-8. These gains were progressive in nature, with the highest quintile of 1993 earners and those originally employed in the formal sector actually experiencing zero or negative growth in their average earnings. The average gain in earnings varied substantially depending on the employment transitions experienced by labour force participants. Obtaining formal sector employment is found to be an important pathway to growth in earnings, yet not exclusively so. The majority of those who get ahead do so by retaining employment in a given sector or moving into the informal sector. The dynamism of the informal sector over this period is shown to be an important contributor to the progressive growth in earnings. Government policies that seek to increase employment and earnings in the informal as well as formal sectors are recommended. Understanding the constraints preventing the vast number of unemployed from engaging in informal employment is shown to be a key issue for future work.
DOI:10.1093/jae/eji001 (Full Text)
Country of focus: South Africa.
Browse | Search : All Pubs | Next


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University of Redlands > Academics >
School of Music >
Faculty and Administration >
Fred Swann
Degrees: SMD, UTS , coursework not completed; Private study in America, France, and England; SMM with distinction Union Theological Seminary School of Sacred Music, NYC, May 1954; BM with distinction: in Organ Performance, Northwestern University, 1952
Frederick Swann, President of the American Guild of Organists (2002-2008), serves as Organist Emeritus of the Crystal Cathedral, Organist Emeritus of First Congregational Church of Los Angeles, and Organ Artist-in-residence at St. Margaret's Episcopal Church in Palm Desert, California.
Mr. Swann, a native of Virginia, holds degrees from Northwestern University School of Music and the School of Sacred Music at Union Theological Seminary, all granted "with distinction". In addition to his prominent church positions, Riverside Church, NYC (1957-1982), Crystal Cathedral (1982-1998) and First Congregational Church of Los Angeles (1998-2001). He was for 10 years Chair of the Organ Department at the Manhattan School of Music and served on the faculties of the School of Sacred Music at Union Theological Seminary as well as Teacher's College of Columbia University, New York City.
In addition to more than 2,000 solo recital presentations in major churches, cathedrals and concert halls throughout North America and abroad, Mr. Swann performs frequently with symphony orchestras and choral organizations. In 2002 he was named Performer of the Year by the New York City chapter of the American Guild of Organists. In 2004 he was selected to perform the Inaugural Recital on the new organ in The Walt Disney Concert Hall in Los Angeles.
Although semi-retired, Mr. Swann is sought after as a leader of organ and church music workshops and is retained frequently as a consultant for new pipe organs, including some of the largest and most prominent in the country.
American Guild of Organist (many national offices – including President) and numerous committees, including magazine editorial over 60 year period); also member of Organ Historical Society and Anglican Association of Musicians; ACDA (not current)
In April 2010, it was designated a Tree Campus USA by the Arbor Day Foundation. Redlands is among just three other colleges or universities in California to receive this designation.
© 2015 University of Redlands. All Rights Reserved.


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Originally written on Fox Sports | Last updated 3/22/13
After an action-packed Day 1 of the NCAA tournament, Day 2 was just as fun, with fifth-seeded Wisconsin falling early and more still to come. Here are some of our favorite highlights from the day: HOW CAN YOU NOT LOVE MARSHALL HENDERSON? Despite an ice-cold 6-for-21 performance vs. Wisconsin, Ole Miss guard Marshall Henderson was still the top scorer in the Rebels' 57-46 win . And, of course, he found time for a few chest bumps. We can't get enough of the many faces of Marshall , and neither can LeBron James. The King offered his kudos for Marshall's free-wheeling play: Man that dude Henderson from Ol Miss got the greenest light in basketball history!! Hahaha. -- LeBron James (@KingJames) March 22, 2013 And Marshall ate it right up: I SUCK AND GET A LEBRON TWEET!!! HAHAHAHA I DONT WANNA HEAR NOBODY SAY NOTHIN, IVE MADE IT!!! -- marshall henderson (@NativeFlash22) March 22, 2013 OH THE MADNESS! After another slow start to the day, the action heated up big time in the aftern...
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- JavaTouch
- Design Patterns
"Software development continues to grow in complexity, and developers must work at
"In many organizations, software development is no longer a cost-center overhead line item—it is an integral part of the company's strategic
Model-Driven Architecture (MDA):
How do you become an Architect?
Modeling provides architects and others with the ability to visualize entire systems, assess different options and rommunicate designs more clearly before taking on the risks.The Unified Modeling Language™ (UML™) is the industry-standard language for specifying, visualizing, constructing, and documenting the artifacts of software systems. It simplifies the complex process of software design, creating a "blueprint" for construction.
- UML home (at OMG)
- Practical UML: A Hands-On Introduction for Developers (from Borland)
- The Value of Modeling (Jun 2004, IBM pdf)
Tech Talks and Discussions
- Who will Develop Software in 10 Years?
Other resources
- UML Resource Home at IBM
Blog Entries
- How do you become an Architect?
Design Tip of The Day


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A collection of news and information related to Muscular Dystrophy published by this site and its partners.
Top Muscular Dystrophy Articles
Displaying items 111-118
Disabled activist, entrepreneur receives national award from Muscular Dystrophy AssociationStory | Nov 7, 2010 | 3:19 AMThomas Arrington III runs a green energy company, advocates for the disabled, and is the primary caretaker for his 3-year-old son Chase. "Use your quiet voice," he exhorts his youngest son, while juggling a business call on his Blackberry and...
Children's hospice in danger of closing
Fighting rare nerve disorder
The Crowd: Jerry Lewis helps raise significant fundsStory | Jun 10, 2010"My father, who was the funniest man I ever knew, told me early in my career to always leave my audience with something warm and meaningful at the end of the show," said comedic legend Jerry Lewis, fronting the "Gift of Hope" annual gala Saturday night at...
Firefighters 'Fill the Boot'
Scott B. Crane, 1987-2011
Medical uses for erectile dysfunction drugsStory | Mar 24, 2010Researchers at Cedars-Sinai Medical Center are testing the medication tadalafil (sold as an erectile dysfunction drug under the brand name Cialis) on men with Becker muscular dystrophy, one of the nine forms of muscular dystrophy, a group of inherited...
Racing for a cureStory | Jan 18, 2011John Graybill Jr. of Bethlehem used to be a model he used to be a wrestler. He used to be a go-kart racer. Then Limb-Girdle Muscular Dystrophy robbed him of those pursuits. It is one of a dozen forms of muscular dystrophy, a progressive disease that...


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Jack Boskett Photography, based in Tewkesbury, provides high-quality photography for your personal and business needs....
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I wish to leave a testimonial to share my first experience with potentially new & regular clients. I walked into the Salon a couple of days ago to be greeted to a warm welcome from the lovely Brian & the team.... Added October 2014
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They provide a 5-star service every time with friendly courteous staff. I wouldn't go anywhere else! Added February 2014
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With a continuing updating portfolio of properties available for rent in Tewkesbury, CGT Lettings should always be your first choice....
A summary of properties to let in Tewkesbury this week from Tewkesbury's best letting agents, CGT Lettings
When you get in touch with your true feelings it helps you understand your role in life. Have you forgotten the goals that you wanted to obtain? Or have you forgotten them? Remember that material success does not always assure Happiness. You have an overwhelming urge to achieve a lot now; however there is a real danger that you will over-estimate your physical drives and run yourself ragged. You may act territorially and aggressively towards others and experience intense power struggles.
At work today you might find yourself in the middle of a slightly sticky situation, don`t take sides. The refusal to take sides will suggest a sense of lack of sympathy toward one of the parties involved, which is something that you do not need right now. Under this influence you have the power to supply a ready answer when challenged and to effectively convince others of your own ideas. However, you may be inclined to jump to conclusions and voice your opinions, before you`ve really thought them through.
Focus your attention on recreational interests and creative pursuits. However this not a good time for taking risks with your money. This is an excellent time for setting up a time-in-motion study. You can improve your efficiency by applying logic and reason to the way you do things, especially at work. Clean up your workstation and tackle your in-tray. Tedious jobs won`t seem so tedious now. During this transit your personal and professional relationships should take a noticeable turn for the better, however you will need to be adaptable with others in order to get the best results.
Any dealing with bankers, insurance agents and realtors are favored. Your luck will come through a friend, and you may be invited on a trip. Partners will work well together. You are more open to the influence of others now, and people will seem favorably disposed towards you. There are opportunities for joint endeavors, which will prove to be mutually beneficial in the long run. However, know that any successes with others now are equated to the amount of goodwill generated between you.
If you allow yourself the chance to grieve a loss even if it is the passing of a time long ago. You sometimes keep your feelings to yourself, but now would be a good time to go ahead and to confess that you too have fears. This will make your relationship so much stronger. There is a restful and relaxing quality to this period. You are more receptive to others and people find you easy-going and approachable. Social get-togethers suit your mood now. You may like to surround yourself with beauty or mingle with artistic people.
Things are back to normal at work. It should be at time for some major work to get finished. Partners work well together and romance is in the air. Passions are intense over this period and any hidden feelings or problems in love are likely to come out into the open now. Emotional intensity is obvious and you can become fixated on achieving personal desires. This can be a trying time for you emotionally; your feelings are being kept in check by the demands of routine responsibilities, which may seem heavier than usual.
You have been concerned about your money situation. If you think that finances are out of control, take some action. You have what it takes to get things back on track you just need to stop making excuses for not doing this. Possibly, you will feel that others don`t understand your needs and that they are not especially supportive. This is not a time for wallowing in self-pity or pessimism. Instead, you need to look at your situation, put your feelings to one side and take whatever practical steps are necessary to move forward.
You are going to be spending most of the day finishing up projects that you have not had the time to complete. Don`t listen to all the rumors that are going around the work place. You might even notice that a relationship is headed for a turning point. Social, creative, artistic and possibly even romantic activities are well-expected now. You feel relaxed and others are at ease in your company. This transit can increase your receptivity to beauty, art and music.
You may be troubled by a dream that you had that was from a past experience. Don`t beat yourself up with what might have been, instead keep the happy memories and move on with your life. You are able to achieve a lot at this time, especially if you put your mind to it. However, inflexible attitudes can create a possible power struggle with someone and you may be inclined to be less tolerant than usual. Travel, creative activity or music can all give you pleasure at the moment.
You have a good accent on your career interests. Still, you must be careful not to take on more than what you can handle. Tonight would be a good night to go and rent a movie or spend your time reading a good book. This is an excellent time for setting up a time-in-motion study. You can improve your efficiency by applying logic and reason to the way you do things, especially at work. Clean up your workstation and tackle your in-tray. Tedious jobs won`t seem so tedious now. A general feeling of well-being and inner harmony exists now.
Talking over a problem with a close friend gives you the perspective that you needed. It is not always easy for you to talk to others about your troubles. But try showing others that you need to confide in someone also. Under this influence you have the power to supply a ready answer when challenged and to effectively convince others of your own ideas. However, you may be inclined to jump to conclusions and voice your opinions, before you`ve really thought them through. Passions are strong now and the urge to enforce love is accentuated.
You have been pushing yourself real hard lately and now it is time to take the day off. It is okay if you take a day off here and there and just slow down for a moment. If you are afraid that someone else is going to grab your piece of pie of success then maybe you should take another look at the way you see things. This can be a good time to re-define responsibilities and boundary lines in your important personal relationships.
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Hi Lee,
Magdalena here - with a small editing job. But this time not for Kippure. I have my own website too: [obscured] Still in its infancy, but getting there...
Please check out the site so you know what I am talking about. We have just added a new walking tour operator directory to the site and we will start calling UK and US based walking- and activity tour operators soon - with a view to entice them to get listed on the site (paid listing).
For this I just got a flyer translated, from German language to English. Original German language flyer attached (PDF).
The translated text now needs to be put into the existing PDF flyer design so that we can then send it to UK, Ireland and US based tour operators (but mainly UK). However, the text I got back from the translator does not read well, it is only a translation after all. See the attached text file, this is the translation.
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Discover what's up in the business of marketing each Friday.
Search In Pics: Google Drive Latte, Google/Bing Traitor Cake & Google Cushions
Barry Schwartz on February 22, 2013 at 12:44 pm
In this week's Search In Pictures, here are the latest images culled from the Web, showing what people eat at the search engine companies, how they play, who they meet, where they speak, what toys they have, and more.
Google Cushions:
Source: Google+
Google Toys:
Source: Flickr
Gmail & Google Drive Latte:
Source: Google+
Google Istanbul Office View:
Source: Google+
Google/Bing Traitor Cake:
Source: Google+
Be a part of the world's largest search marketing conference, Search Engine Land's SMX East. The robust agenda covers the latest tactics in paid search, SEO, mobile, analytics and more. Register today and save $300, or come as a team and save 10%-20%.


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Dr. Edward Baruch is a psychiatrist in Mount Laurel, NJ. He cares for the psychological well-being of patients, treating conditions like depressive disorders.
Learn More
We invite you to write a review about your experience with Dr. Baruch.
Find potential causes and treatment options with the MD.com Symptom Checker.
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Crime, courts and legal issues in Milwaukee and throughout Wisconsin
Slayings and near-slayings, while the cops are low on bullets
This morning's papers brought a host of information about killings and situations that came quite close to being slayings, with a pair of Milwaukee shootings involving reckless central-city gunplay accompanied by two outstate cases that each allege a husband murdered a wife. And amidst all this violence, we encounter a report Wisconsin's police are low on ammunition.
This is our daily summary of Wisconsin court-related news in the Journal Sentinel and elsewhere. Check this space each weekday morning for a quick digest of the state's legal happenings, and send your news tips here.
- In Milwaukee's courts yesterday, a teenager went to prison for wildly shooting down a street and nearly killing a 12-year-old family friend, while a 40-year-old man told the cops he had an Andre the Giant-size quantity of cognac in him when he shot five people in a North Ave. bar last week, according to a murder charge.
- That's a lot of shooting. What great timing for the police to report a bullet shortage.
- Gerald Boyle got a jailed homicide defendant access to more documents about an alleged November domestic-violence killing from Ripon.
- Meanwhile, a whole team of high-profile defense lawyers is asking to bar all mentions of cadaver dogs in the case of a 30-year-old Madison disappearance that's about to become a murder trial. The dogs didn't find any remains, they posit, so they don't want to let the jury hear about the "alerts" that came up.
- "Taste potentiators," "flavor profiles" and "roasted meat notes in a gravy"? Wow, this trademark lawsuit between flavor manufacturers really has a lingo that doesn't come up in court much.
- And down in Chicago, the "Family Secrets" mob trial once again drags our fair state's name into it, with one reputed mobster claiming $2 million was lifted from his (unnamed location in) Wisconsin home.
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The Top 10 In Action Sports
01Brick By Brick: Camping Lego Style
02Booze and Bikes: 14 Tours That Let Combine Two of the Best Things in the World
03Who Needs Hollywood? These Incredible Videos Were All Filmed on the Simplest Cameras
04Sam Pilgrim vs. The World: The Champion Aiming To Reclaim His Crown In A New Era Of Biking
05Eccentric Adventures Episode 2: Britain's Most Brutal Illegal Event is All About Cheese
06A Journey Into Darkness: We Went Mountain Biking in the Abandoned Mines of Slovenia
07After the Apocalypse: Inside The World's Most Breathtaking Ghost Towns
08Debate: Let's Stop Hating On Parents Who Want To Raise Adventurous Kids
09Guns, Roses, And Eating Insects: Adventure Cycling in Vietnam
10From Intense Trails to Intensive Care: Dicing with Death In a Mountain Biking Paradise
Powley's Angels - Extras
A Skateboarding video by vansuk - 20,519 views
Vans Extras edit from the Big Push 2009. Featuring Joshua 'Manhead' Young, Chris Oliver, Ben Grove, Kris Vile and Ben Nordberg. Special guest star Dougy McLaughlan and of course the enigmatic Powley. Just a taste of the full Vans Skate edit from the Big Push 2009 'Powley's Angels' now available cover mounted on the latest issue of Sidewalk mag.
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