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The new motto of the Republican Party seems to be, "If you can't win, rig the game." In just the past few years, we've seen Republicans push voter ID laws that are meant to prevent young people, low-income people and people of color from having their say in elections. They have tried to keep likely Democratic voters from the polls by placing limits on voter registration and early voting. And Republican gerrymandering has become all too familiar: just this year, Virginia Republicans pulled a 'dirty trick', trying to redistrict their state while the Democrats' backs were turned.
Now, Republicans have a new plan: rigging the Electoral College. Bills have been introduced in six states, and failed or stalled in five of them. But Pennsylvania Republicans are forging ahead. On February 21, state Senate Majority Leader Dominic Pileggi introduced Senate Bill 538, which would fundamentally change the way Pennsylvania allocates its Electoral College votes. Pileggi's plan would split up Pennsylvania's 20 electoral votes, awarding them in proportion to the popular vote in the state, plus two for the winner. In 2012, President Obama won all 20 of Pennsylvania's electoral votes. Under Pileggi's system, he would have won just 12. Eight electoral votes could change the outcome of a close election: just think of what happened in 2000.
What you can do if you live in Pennsylvania:
If you live in Pennsylvania, Majority Leader Dominic Pileggi and your State Senators need to know that Pennsylvanians won't stand for these dirty tricks. Look up your state senator's contact information here.
Conversation Guidelines:
•Always be polite. You will most likely speak with an aide, who will record the information and relay it to the Representative.
•You might be asked to provide your contact information. This is so that the office can follow up with you if there are any questions. Sometimes offices will send a follow-up letter as well.
Possible call script to Dominic Pileggi:
"Hello. My name is ______ and I'm a Pennsylvanian. I'm calling to let Majority Leader Pileggi know that I do not support SB 538, which would change the way the state allocates its electoral votes and unfairly rig it in favor of Republican candidates. The bill would make Pennsylvania, its issues, and its residents less important in Presidential elections. I urge you to vote against Senate Bill 538. Thank you for your consideration."
Possible call script to your State Senator:
"Hello. My name is ____ and I'm a constituent of Senator _____. I'm calling today to ask the Senator to vote against Senate bill 538 that would change the way the state allocates its electoral votes and unfairly rig it in favor of Republican candidates. The bill would make Pennsylvania, its issues, and its residents less important in Presidential elections. I urge you to vote against Senate Bill 538. Thank you for your consideration."
You may also wish to provide some detail as to why you don't support the provision. Here are some suggestions:
- Sour grapes: The bill represents a sour grapes attempt on the Republicans' part to fix the Electoral College in their favor. Their loss in 2012 doesn't entitle them to try and change the rules to make it easier to win. Elections should be won and lost on issues, not by gaming the system.
- Pennsylvania matters: If the bill passes, Pennsylvania will become less important to Presidential elections. That means less attention to the issues that matter to Pennsylvanians. Pennsylvania's diverse communities are a bellwether for the American electorate, and they deserve to have their say.
- More debate: This issue is too important to be rammed through a single-party legislature and executive branch. Republicans might control both the legislature and the Governor's mansion, but that shouldn't mean they can fix the game in their favor. Decisions like this should be made slowly, in public, and on a bipartisan basis.
Submit a letter to the editor:
- Philadelphia Inquirer: email@example.com, with guidelines on submitting a letter here.
- Penn Live/Patriot News: firstname.lastname@example.com
- Phillyburbs.com (Courier Times, The Intelligencer, Burlington County Times) firstname.lastname@example.com
Tips for writing letters to the editor:
- Be brief. 150-200 words is usually the ideal length.
- Keep it factual, and keep it focused on this issue. Strong letters that take on one issue are most likely to be published.
- Include your contact information.
Why it matters beyond Pennsylvania:
Republican legislators in Virginia, Florida, Ohio, Wisconsin and Michigan have also proposed overhauling the way their states apportion electoral votes. It's not an accident that these states are all closely-fought battleground states, worth a total of 106 electoral votes: even changing the way just one of these states allocates its electoral votes could be enough to alter the outcome of a close election. Right now, the bills in these states have stalled, but if the Pennsylvania bill passes, Republicans in these other states will be emboldened by its success. If you think it's a bad idea to have Pennsylvania's electoral votes rigged to favor the Republicans, imagine if it happens in two or three states- or all six.
What you can do if you live outside of Pennsylvania:
Sign our petition to show that Americans want a fair election fought on the issues of the day. Americans expect a fair debate and it is important to let your voice be heard.


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With the 2013 NFL draft order all but set heading into the Super Bowl, it's time to take a fresh look at the players teams are targeting.
A mock draft is much more than just assigning the best player to the next team on the list. When sitting down to write a mock draft, I'm taking my own personal evaluations of players plus news and notes from NFL scouts and executives that I'm in contact with.
Picks are assigned with free agency, team needs and team schemes in mind. Who should your team be looking at? Find out in our new three-round mock draft.

subset: commoncrawl


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Perkins Loan Services
As of June 30, 2013
Due to loan funding changes, North Idaho College has assigned it's outstanding Federal Perkins Student Loans to the Department of Education. Students with Federal Perkins Loans obtained through North Idaho College should contact the Department of Education at (800) 621-3115 for further information.
Thank you.


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Tuesday, May 27, 2008
Weekend Updates
How was your long weekend? Mine was fabulous! It was nice to relax and enjoy not working, he he.
I had half a day on Friday so I was able to get a lot done. I saw an early showing of Indiana Jones-Kingdom of the Crystal Skull. I loved that movie. Not only did it crack me up but I think I was the only one in the theatre screaming every time there was an intense action scene.
Afterwards, a few friends and I stopped by at MAC and I was able to pick up the new M.A.C Collection-Neo Sci-Fi, Solar Fields, and Future Earth.
Here's a video review I did this weekend.
I'm going to do a post with swatches tonight of comparable colors…woodwinked, bronze, satin taupe. That way you guys can see them in person.
All in all, thumbs up on the collection. The colors are all really pretty. I'm more of a bright eyeshadow girl but I can appreciate the gorgeous gold and bronze shades in this collections. I also loveeeee the bright orange lipstick, electro. I wore it out this weekend and rocked it! I also wore it with bronzescape and talk about shimmery! It was gorgeous. I actually paired it with my Milani Color brilliance liner in green and it looked really cool.
Saturday was decorating day. I also finished up most of the decorating this weekend. It was the Bf and I's gazillionith grip to Ikea. I'm only missing a few random pieces (nightstand lamp, drawer pulls) that I can wait for my wallet to recover. Hopefully I'll get some pics up soon.
Sunday we had brunch with my friend's parents who were in town. I had a lox bagel combo with fresh fruit, yum! I also had to go back to Ikea to return something and pick up more stuff! The rest of the night I played with makeup and relaxed.
Monday-Memorial Day.
I woke up early to do a makeup lesson session. The client was going to turn 50 and traveling to Jamaica for a huge party. I taught her how to do one side of her face and she duplicated the other. We went for a gold/smokey look. It was a dramatic before and after! The power of makeup is unbelievable. I'll post pics soon.
Afterwards, my friends and I decided to play like we were grown ups and put together a nice little barbeque. Talk about too much food! We had hot dogs, veggie burgers, turkey burgers, beef burgers, bbq chicken, marinated chicken, pasta salad, watermelon, potato salad, corn on the cob, and ice cream! Needless to say, we all have some major leftovers. We then had an intense game of scattegories, lol, watched Keeping up with the Kardashians, and called it a night.
I'm going to try and get a Neo-Sci Fi look done tonight. I haven't quite decided on a look, so I'll leave it up to you guys to decide. Hopefully I'll have it up by tomorrow. I'll be going out of town for the second half of this week. I'm heading up north to NY for a bachelorette party and some shopping and Connecticut for a wedding. I'm going to do my best to stay on my budget!
Stay tuned for things to come:
-Kim Kardashian Tutorial (filmed, needs to be edited)
-Kat Von D Tutorial (filmed, in editing process)
-False Lashes Tutorial (filmed, in editing process)
-Coastal Scents haul and review (filmed, needs to edited)
-Neo-Sci Fi Tutorial (needs to be filmed)
-Blue and Green Pigments Video (done, needs to be uploaded)
Till next time, ciao bellas!
8 comments:
- PBW said...
Looking forward to your Neo Sci-fi post and video.
And for my order from MAC
- May 27, 2008 at 3:01 PM
- yummy411 said...
you are one busy mama! sounds like you had a great weekend and wonderful posts to come. i can't see the neo sci fi review right now, but look forward to it and the look!
oh yes yes the makeover shots too!
- May 27, 2008 at 4:08 PM
- Yellow Fever said...
awesome ren! i'm totally looking forward to the swatch comparison b/c i think i might have dupes for everything except magnetic fields. thanks girl!
- May 27, 2008 at 5:00 PM
- Ethereal Prey said...
wow looks like you had fun! do half of my face and teach my how to do the other half! :P you are a busy girl. post pics soon!
- May 27, 2008 at 5:35 PM
- mandilicious said...
- This comment has been removed by the author.
- May 27, 2008 at 11:17 PM
- mandilicious said...
ooh wow!..you have so many upcoming videos..i'm excited!..i watch your videos before you even post them here..i love your videos..you seem like a really really nice person!..that's honest truth!..no BS..lol..that's how i feel every time i watch your vids!
- May 27, 2008 at 11:19 PM
- MakeupByRenRen said...
pbw: he he, i bet you are!
yummy: oh hecky yah, i'm posting those makeover shots this week
yellow fever: i just put some swatches up!
ethereal prey: will do mama!
- May 28, 2008 at 11:38 AM
- Beauty 365 said...
such a fun weekend!
Beauty 365
Beauty Every Day
- May 30, 2008 at 1:27 PM


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"Sportstalk" with Bobby Hebert and Deke Bellavia
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Steve: Could Travaris Cadet be the new Darren Sproles?
by Steve Geller
posted Jun 13 2014 1:47PM
Even with the departure of Darren Sproles, the Saints running back corp remains loaded with talent this year. Pierre Thomas, Mark Ingram and Khiry Robinson headline the group, while Travaris Cadet is entering his 3rd year with the team, and is looking to expand upon his role, which has been limited thus far.
Out of the four guys I just mentioned, only Ingram was selected in the NFL draft. The other three are all undrafted free agent finds by the team.
"It's just like Coach Payton says; it doesn't matter how you get here, it's what you do when you are here," says Cadet. "It's all about gaining respect in the locker room and from the coaches."
So far, Cadet has really just been involved with special teams on the Saints. He has acted as a returner and also covered on kicks. But, now that Sproles is gone, Cadet could easily be that pass receiving threat out the backfield.
"I just try and take advantages of my opportunities. You know, I'm here for a reason; I'm not here by mistake. I don't want to waste any days, because the day that you waste you can never get back."
Now, Cadet is a much bigger player then Sproles. He stands 6 ft 1, 210 pounds, but has a similar skill set. He is fast, elusive and a great pass receiving threat out the backfield.
So, could Cadet run basically the same plays as Sproles?
"I think a year ago, I don't know that I would have been able to tell you that," Coach Sean Payton responded. "The focus for him was the running game per se. That element with regards to running routes and catching the football, he would be further ahead, but we saw him last year as a guy who transitioned into someone that we handed the ball to. That's something he's worked hard on. He's a guy with good hands, he's sudden with a good change of direction, and I think that is one of the things we'll look for in this upcoming training camp. He's been able to do a lot of the things we've asked Darren to do in the passing game. You just keep building on that. He's a good young talent."
Cadet hasn't seen much action in 2 years in Black and Gold though. He has just one carry -
one career carry -
for 5 yards, with 7 receptions for 49 yards and 1 touchdown. His standout performances in organized team activities and mini-camp need to carry over into the preseason in order for him to have any hope a gaining a more active role in the offense.
Cadet seems ready of the challenge though.
"I feel like if you dedicate yourself to whatever you do in life, you put the overtime in and you don't get complacent though success and through hard times, you'll be the player God wants you to be."
Photos via Chris Bennett
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Victoria wrote:...And those were added to the line up when the hot topic was the tasting comparison program. Which sadly, never happened.
kymidwife wrote:If Adagio ever does finally decide to offer a gaiwan in their teawares section, I'd love to see Zack demo how to use a gaiwan for brewing in one of the TeaV episodes... would be nice to see him showing alittle "how-to" in addition to the tasting. New tea drinkers may be intimidated by brewing, and would benefit from seeing the simplicity of a "regular guy" using something like a gaiwan.
kymidwife wrote:Zack's how-to-use-a-gaiwan video
Dresden wrote:kymidwife wrote:Zack's how-to-use-a-gaiwan video
Where do I find this?


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Whether you�re a frequent traveler, an outdoor enthusiast or a city dweller, we�ve scoped out the best dog breeds for you.
You�ve already fallen in love with that puppy�s sweet face, her beautiful fuzzy coat, the way she licks your face. But before you give in to those big brown eyes, is this pup really the best dog breed for you? �Nothing takes the place of planning, preparation and research by a family getting a dog,� says Clark Fobian, DVM, President of the American Veterinary Medical Association and a veterinary practitioner in Sedalia, Missouri. �It�s important to match a dog to your lifestyle and your environment�and then think about breed.� Although dogs within certain breeds share characteristics, training goes a long way in shaping almost any dog to be the companion you�re after, says Fobian. Nevertheless, to begin narrowing your search for the perfect hound, here are suggestions of breeds that may fit one lifestyle better than another. The best breed for runners, hikers, outdoorsy people: �Look for a dog that�s meant to be active�herding breeds and hunting dogs,� says Nancy Scanlan, DVM, executive director of the American Holistic Veterinary Medical Association. �A Whippet is good, but you have to keep it on a leash. Labradors and retrievers are more reliable than Whippets off a leash.� The best breed for swimmers, fishers, beach goers: When you think beach, think about the dog�s coat, says Fobian: �Labs and Golden Retrievers shed sand and water. You want a high activity dog that requires regular and extensive exercise. The whole line of retrievers and setters would make good water dogs.� Standard poodles like to swim too, says Scanlan: �But they�ll need a short kennel clip because their fur can mat if it�s waterlogged, and then it�s hard to get dry.� The best breed for frequent travelers: Think small and quiet, says Scanlan: �Dogs that can fit into small spaces are the �toy� dogs: Toy poodles, a small Lhasa Apso, or Shih Tzu.� Chihuahuas are the right size, but they can be yappy, she says. �It�s hard to imagine a breed that could not be trained to travel comfortably,� says Fobian. �You have to accustom them to honking horns and sirens and make sure they can settle down in a car.� You can help your dog do that by exercising him before a trip, making sure he�s not overfed or watered before the trip, and crating him with a favorite chew toy. The best breed for grown-ups with kids: �Labs and Golden Retrievers are great because they are so tolerant you can even poke them,� says Scanlan. �Newfoundlands are tolerant too and good at guarding kids, but they are huge so you have to consider the size of your household.� The best breed for older adults: �A large dog can pull an elderly person over if she is unsteady, so smaller dogs are better,� says Scanlan. �But if someone is older and active, a Jack Russell Terrier or a Schnauzer is a good choice. Miniature or toy poodles are intelligent, people-oriented lap dogs. But poodles and Schnauzers require grooming, so if a person can�t take them for that, a short-haired terrier is a good choice.� The best breed for apartment or city dwellers: For small spaces, smaller breeds are better, unless you like to walk a lot and are close to a park, says Scanlan. Otherwise, think toy or miniature poodles, or Lhasa Apsos. �A Cocker Spaniel is good choice too, although it has to be groomed.� Fobian�s choice is a Boston terrier: �They are so adaptable.� The best breed for people with allergies: You could go with the Obamas� choice: A Portuguese Water dog, says Scanlan: �The best dogs for allergies are hairless guys�the Chinese Crested that has a fuzz ball on top of its head, or a Mexican hairless dog--because they don�t have hair or dandruff, but [aesthetically], they take some getting used to.� The next best are dogs with curly hair that don�t have a longer outer coat: a Bedlington terrier or a poodle. The best breed for stressed or depressed people: Some service dogs are trained to help people who have anxiety and/or depression, says Scanlan: �Research shows that people with either of those conditions are helped by having a dog they can touch. And dogs pick up on those feelings and comfort them. Labs and Great Pyrenees make really good service dogs.� For more information, go to Mental Health Assistance Dogs, www.mentalhealthdogs.org or the National Service Animal Registry, www.nsarco.com. Brought to you by: Spry Living


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Backyard Vineyard Consulting
I have found web surfing to be fraught with peril, lately. The most innocent of mouse clicks may result in a virus or malware. I consider myself a pretty wary user, and I have avoided permanent troubles, but I have lost a couple evenings of rebooting and cleanup over the last year.
In any case, while randomly surfing, I came across the interesting (and safe) web site of a Perinton-based "backyard vineyard" consultant, Woods Wine. "As few as 12 vines can provide a bottle of wine for every weekend of the year," says owner Ed Kwiek. Look also for the blog with videos, although Ed seems to be taking a blogging break during the off season.


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Our Services, Aims and Policies
Research Service at North Devon Record Office
The Research Service at North Devon Record Office has been discontinued. This is due to recent budget cuts and the need to rationalise the work of the archive service.
However, we will continue to deal with Freedom of Information requests and these will be dealt with through our general enquiry service. There will be a charge for these enquiries at the rate of £15 per 30 minutes and £30 per hour.
We thank customers who have used the Research Service in the past and regret that we are unable to deal with any further genealogical, historical or property-related research requests.
Further research of this kind is now being undertaken by the North Devon Athenaeum staff, and private researchers. Details of these can be obtained as follows:
North Devon Athenaeum, which is located on the same floor of the library building as North Devon Record Office.
Postal address: North Devon Athenaeum, Tuly Street, Barnstaple, EX31 1EL, Devon
Website: http://www.northdevonathenaeum.org.uk/
Email: email@example.com
Devon Family History Society, which maintains a list of researchers willing to undertake work in the record office.
Postal address: Devon Family History Society, P.O. Box 9, Exeter EX2 6YP, Devon, United Kingdom.
Website: http://www.devonfhs.org.uk/
Email: email@example.com
The Association of Genealogists and Researchers in Archives (AGRA) – members of this association are experienced researchers in genealogy and other fields of historical research
Postal address: Enquiries – AGRA, 43 Bowes Wood, New Ash Green, Longfield, DA3 8QL, United Kingdom
Website: www.agra.org.uk To make a general enquiry, use the on-line form on the AGRA website.


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AC Powered
Patriot - PE5 Fence Energizer - 0.20 Joule$47.99 As low as: $43.19The Patriot PE5 is a 110 volt a/c plug in 0.20 joule model. This is a small energizer ideal for fencing small properties up to 20 acres. Learn More
Earn 47 Points
Gallagher - M50 - Rustler - Electric Fence Energizer/Charger$75.00 As low as: $67.50This is an excellent small 110 volt energizer with 0.5 Joule stored energy that will power up to 20 acres or 3 mile of fencing. It is easy to install with a sturdy wall clip and has superior lightning protection built in. Learn More
Earn 75 Points


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Application for UK visa to visit or for short-term stay: form VAF1A
Form to apply to visit or transit through the UK, for short-term study and parents visiting their child on a Tier 4 (child) visa.
Use this form if you are outside the UK and cannot apply online. It is to apply to come to the UK as a visitor or transit through the UK. It is also for short-term students and parents coming to visit their child on a Tier 4 (Child) visa.
Read the guidance notes on applying for a UK visa using VAF1A form before applying.
Further information on visas, including whether you are eligible and how to apply, is available in our visa guides.


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I'm not a guitar person. I know what I like when I hear it. I did see Paul in 1990 in Boston, filming his DVD and between takes the band jammed and I was totally impressed by Paul's bass playing. I have heard a lot of people say he is an okay bass player but after that, I will take anyone who says that out back and stomp the stuffing out of him or her.
I can play the radio as I have stated before. George is good but then I have not focused in on his playing but I would not say John is but I do agree with his writing ability and his rock n'roll voice. But I really don't zoom in on any one instrument when listening to a song.


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beautiful and soft curly brown hairstyle
There is a romantic feel about this look at this young woman has her hair long and curly. The hair at back falls into curly ringlets with a slight curled bang at front. The look is chic and a nice style for a prom or homecoming.The cut for this style is between medium and long in length.This hair colour is a dark brown with rich and shimmering shades of lighter brown.
Model Bride


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Our good friend Debbie is due to come up to perform at the golden hour on wed. the 21st. I invited her to come with the idea we'd pay for her cheap train ticket. WELLL.... it looks like she left it too late and has now aquired a £50 train ticket.
So, I'm hoping the good events people will approve this expenditure for Debbie (and to make it so i don't have to pay out of pocket.)
I can rationalize this in another way, as well: Debbie will be looking after our theatre porjects this summer (should we choose to have any) and we can set up a meeting on thurs to dicuss this if people wish?


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Robotic Thoracic Surgery
Robotic surgical technologies have already started to change the way surgeons operate inside the chest – in particular for procedures performed on the lungs and esophagus.
The "Dylewski'" technique, performed only by surgeons at Methodist University Hospital's Center for Minimally Invasive Surgery, involves using the da Vinci® robot to perform a safer, more precise lung lobectomy.
While a traditional open thoracotomy operation requires surgeons to make a larger chest incision and spread or cut of the breastbone or ribs, the "Dylewski" technique uses only four incisions to remove the effected lobe below the ribs. The one-centimeter incisions on the chest are in the same rib space, thus limiting pain because only one rib space is effected, as opposed to three rib spaces in a video-assisted lobectomy or open thoracotomy procedure.
The "Dyleweski" technique allows for portions of the rib go virtually untouched by the robot and surgery length is shorter; two advantages not possible with an open thoracotomy.
The da Vinci® Surgical System provides surgeons with an alternative to both traditional open surgery and conventional laparoscopy, putting a surgeon's hands at the controls of a state-of-the-art robotic platform. Equipped with high definition, three-dimensional imaging capabilities, the da Vinci® Surgical System enables surgeons to perform thymectomies and other potentially traumatic procedures through 1-2 cm incisions, without spreading or cutting the breastbone or ribs, thereby minimizing blood loss, pain and scarring.
By dramatically enhancing visualization, precision, control and dexterity, the da Vinci® Surgical System overcomes the limitations of traditional thoracoscopic technology, helping physicians to perform complex surgery in a manner never before experienced. With enhanced surgical capabilities, physicians are now able to extend the benefits of minimally invasive surgery to the broadest possible range of patients.
Benefits of Robotic Thoracic Surgery
Complex procedures like thoracic surgery require an excellent view of the operative field and the ability to maneuver instruments within the chest cavity. Thoracic surgery performed robotically provides better control, dexterity and visualization than with an open procedure, allowing surgeons to offer patients the benefits of minimally invasive surgery, including:
- Shorter hospital stay
- Less pain and scarring
- Less risk of infection
- Less blood loss and fewer transfusions
- Faster recovery
- Quicker return to normal activities
To find a thoracic surgeon in Memphis, Tennessee, please use our physician locator or call 888.777.5959.


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Peppard: Beatles spawn James McCartney books a spring stop in Dallas
The daughters of Sir Paul McCartney and the late photographer Linda McCartney have always gotten a warm welcome in Dallas, so now their brother, James McCartney, is ready to test the local hospitality.
Releasing his first full-length album, Me, James is heading out this spring for a 47-date tour of intimate listening venues to promote it. In Dallas, he's scheduled a solo acoustic show on May 1 at the Kessler Theatre.
James' photographer sister, Mary McCartney, was in Dallas a few years ago for a successful gallery show at the Goss-Michael Foundation (Sir Paul sent flowers). And, few can forget fashion designer Stella McCartney's triumphant arrival at the NorthPark Neiman Marcus where she was greeted by the Carter High School cheerleading squad and 500 guests. Last year, Stella opened a retail boutique in Highland Park Village.


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Kingston 1GB PC2700 - $30 shipped
Digicam - again, nothing wrong with it, just looking for an upgrade. Looking to get $130 including shipping:
HP Photosmart 945
HP Photosmart 8881 Digital Docking Station
Two 8" Digital Reference subs in custom box with 2 amps - looking for $125. Local pickup only (located in Elyria). I had this setup in my Fiero, and it hits hard despite the small size. Perfect for small cars. Box stands up behind passenger seat, and I had the amps mounted to the firewall behind the driver's seat. I can email pics upon request.
Paypal is highly preferred.


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Media Watch | Good Morning America Show Us The Pacific Garbage Patch
Contributing Monkie G Living Staff Monkies
Published on June 7, 2009
Section G/Videos, Green Report / Media
America and the world are finally waking up to the massive trashing of the oceans. About a year ago, we posted our first story on the problem and since that time, it has been picked up everywhere. First on Oprah and now on Good Morning America. Lets hope all this exposure will mean something. We know we can see the actual surge of traffic to gliving.com, as the shows are seen in each new country.
Good Morning America: The world's largest trash dump doesn't sit on some barren field outside an urban center. It resides thousands of miles from any land in the Pacific Ocean.
Bottle caps, soap bottles, laundry baskets and shards of plastic are just a few things that float in the ocean's vastness. Known as the Great Pacific Garbage Patch, the "dump" is composed mainly of plastic, which isn't biodegradable.
Instead, the plastic breaks down into smaller and smaller pieces in the patch that extends thousands of miles, from California's coast to China. Charles Moore, who discovered the trash heap by accident in 1997 when he was sailing the Pacific, collects samples of the growing garbage bin. Some of his samples have contained six times more plastic than plankton.
"It is like a minestrone and … a lot of the vegetables are plastic," said Moore, who stages regular trips to the garbage patch for research.
Video after the jump


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Course: Main Course, Appetizers
Products: Toaster Ovens
Looking for an affordable and convenient, not to mention quick, appetizer idea for parties and get-togethers? Read more about Wonton Cups on our Everyday Good Thinking blog.
Serves: 6
TEST KITCHEN TIP: For savory cups, sprinkle brushed wrappers with a combination of Parmesan cheese and Italian seasoning. For sweet cups, sprinkle with cinnamon sugar. Fill warm cups with items such as scrambled eggs for breakfast or fill cool cups with chicken salad for lunch or pudding or mousse for dessert.


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As a young woman growing up in Louisiana, a career in the Foreign Service was never really on my list of life dreams -- but all that changed, beginning with graduate school and a research project in Africa that opened my eyes to the possibilities of diplomatic life.
Since joining the Department of State 31 years ago, I have lived and worked on four continents, traveling the world from Afghanistan to South Africa. I have witnessed the horror of genocide in Rwanda; I've celebrated the joy of people coming out of 15 years of war to elect the first woman president in Africa. I've never regretted those first steps out of my comfort zone and into the world of diplomacy.
I've been the face of America abroad, and I've been blessed with the opportunity to make a difference in people's lives and to represent my nation. The State Department needs the energy and passion of Americans who want a career that matters.
And that's why we've made this video.
We want to highlight and share with you some of the faces and stories of the amazing people who have made their dreams to do good in the world a reality through their career in the Foreign Service.
I hope you will watch it and think about this unique career and lifestyle. You can see the full film by visiting careers.state.gov, where you'll be able to delve much deeper into the various types of diplomatic careers and learn about the steps you can take to pursue this path.
Matt in Wyoming writes:
That is a very lovely film. Being a year into the hiring process, it can seem long and, at times, it is disheartening. This has served to remind me of that light at the end of the tunnel, so thanks for that. Just give the call and I'll be there. Cheers.
Kamal E. in Washington, D.C. writes:
Gino D. in New York writes:
Excellent clip! I'm taking the FSOT in February and I've interned twice in Europe. Best government department on the planet.
Judith C. in the U.S.A. writes:
From the age of 16 my daughter wanted to be a FSO and has tenaciously followed her dream. At last her dream came true! Last May she was sworn it as Foreign Service Officer and will go to Juarez Mexico in April. We couldn't be prouder.
Alice in Kansas writes:
Great video but I think it would have been beneficial to highlight the Foreign Service Specialist opportunities like medical, diplomatic security, and information management.
Sarah in Texas writes:
I agree with Alice in Kansas, Foreign Service Specialists opportunities weren't mentioned. Specialists are members of the Foreign Service too, including Office Management Specialists.
Dinorah F. in Nebraska writes:
Very inspiring video; this is the type of jobs I like to do. A job where I can make the difference and see the results of my labor.
Alan M. in Florida writes:
Even though I have never been a part of the Foreign Service, I have been teaching in China for almost two years. I saw the film, read your materials on China and wondered if I am like a member of the Foreign Service due to the attention I receive from the leaders,staff and students. I also have a Foreign Expert folder from the PRC. Since I am 61 years old,I not able to serve my country through the Foreeign Service. Thank You Am


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Israel Poised to Ban Fur
With the weather warming up, a lot of fur-wearers will be retiring their pelts to closets and vaults until autumn. But that doesn't mean that "fur season" is over.
Consider this—right now, the following is happening around the world:
- Baby seals are being shot and beaten on the ice floes off Newfoundland and Labrador in Canada.
- Also in Canada, mother bears are in danger of being shot—leaving their cubs to starve to death—so that their fur can be used to make pointless ceremonial caps for The Queen's Guards in the U.K.
- Animals on fur farms are being packed into tiny cages, going insane from stress and captivity, or being poisoned, electocuted, or even skinned alive.
- Elsewhere, wild animals—or perhaps your cat or dog—are caught in cruel steel-jaw traps, terrified and in anguish.
But while those winter coats are forgotten about for a few months, there are some people who will still have fur on their mind this summer, including the entire nation of Israel. Israeli Knesset Member Nitzan Horowitz has introduced the world's first nationwide bill to prohibit the fur industry. If it becomes law, this bill would prohibit the production, sale, and importation of all fur products throughout Israel. Very cool news for a hot season!
Check out PETA Asia Pacific's site to encourage continued support for this historic bill. And if that just whets your appetite for some serious warm-weather fur-fighting, check this out too.
Written by Jeff Mackey
Commenting is closed.
Yeah makes fur illegal! I wish fur was illegal in America and Canada too! I think fur on people is ugly. I think that if you wear a wild animal, you might as well being wearing your beloved pet, it's the same thing and all animals feel pain, sorrow, and suffering, just like love. But so many animals in the world don't feel love. No one has ever loved or cared about or for them. This is wrong and we need to put an end to fur farms and animals being used for fur and skin. I am Jewish and I have made my Hasidic Jew family members stop wearing fur. It's not for religion that is worn. It's just another tradition like Amish-ism (wish really isn't a religion, but more of a way of life).
This is fantastic newsbut every country needs to implement this total ban on real furit is so true what another person wrote on herethat we are a country of nosy parkers and that we like to know what is going on in other peoples lives but when it comes to torture and brutality on innocent animals in other countries we turn a blind eye and dont want to know! shame on us human beings for doing this!! animals have no voices they need us to speak for them. I pray to god soon in time these sick fur farms get shut down forever.
This is wonderfull! I hope and pray that this bill passes I hope other countries soon follow Israels foot steps We need to stop this horrible crulety in the name of fashion!
W00t! Go Israel. It's sad some people on here are hating… if you want to talk human rights go look at how Jews are treated in other Middle Eastern countries. Israel can always improve in that reguard but so can the US Iran Ethiopia England and every single country in the world. As someone who has actually visited let me tell you. I have not seen one person wearing fur not even fauxfur. There is also virtually no resteraunt or eatery in Israel that doesn't carry at least a vegetarian if not vegan meal. I also didn't need glasses to read long lists of ingredients full of weird "monoanddiglyceride" crap. They also have some banging animal rights protests the heat makes nudity way more comfortable too. Thanks PETA2. It's not everyday I hear good news about where half relatives live
Israel will make an interesting subject…
We will also ban fur. and shut down the fur trade in the middle east.I'm looking for reponses in comment form but first please read my brother's other comments. Good Day AshurbanipalII brother of the heir
Help!!!Save us and our loyal animal friends from our sworn enemies and the eneimies of every middle eastern animal the kurds SPITWe must act now if we are to stop them!! From killing of all of Iraq's native animal speices they consider them delicases yech For centuries we have been against meat Sargon III heirofmespatamia
P.S. HTML HaHa
Please help us rebuild the great nations of assryia and babylonia. For centuries my people have beens slauqutered and we are more than willing to help find more "Ethical" ways of treating animals for example we optain animal hair and transform and multiply the cells once our nations are reformed we will give much to PETA in return like donations our heartland was once in sudan so we ask PETA sets up shop their. Good Day Sargon III Heir of assryian and babylonian royal family
To answer the question below Israel will be able to stop defending its right to exist when Hamas terrorists stop trying to destroy Israel and stop keeping Palestinians under Hamas's fundamentalist idea of Islam which is totally unethical and cruel to both human and animal. "Posted by Lori May 29 2009 0204 PM What a wonderful thing that Israel is proposing to do. I just wish they would stop oppressing the Palestinian people as well."
Everybody is right if they ban fur trade completly it willgive the boost for other contrys need to ban all fur making and trade. If you kill an animal you must eat it and use all of its body dont waste a thing…. if you arent in need for food LEAVE ANIMALS AND THERE FURS ALONEE!! THEY NEED THEM MORE THAN WE DO. Melissa
Hi all I am smiling and have a good feeling in my heart for I wrote the article quoted here above on our bill to ban all fur trade in Israel and the vast majority as your comments are thoughtful feeling and supportive. I am glad too that almost all of you understand the high level of this important path and that it is all about the animals and nonpolitical but what I hope is but the first step on a global path of enlightenment towards animals. Thanku to u all and peace and light to all
Bravo Israel. It will be a great decision and an example for all other countries Thank you for your compassion Dalila
OMG!!! Israel ROCKS! I am very connected to Israel and Jewish people have always cared a lot about animals. The laws of Kashrut forbid eating many kinds of animal so all thats left after this law is passed is poultry fish and beef.
Google 'kosher' before you praise Israel. This is just as bad as the fur industry. And harriet the purposeful annoyance helping unfortunate people has nothing to do with the fur trade in Israel not that Israel will help people nonJews the ones suffering but this is an entirely unrelated subject.
Israel should start focusing its energy on taking care of its people and suffering neighbors before it can even think about stopping fur. Does someone have their priorities mixed up or what?
God bless Israel. If greed wasn't the first thought in most people's mind we would have a more gentler and compassionate world to live in. It's time we put people and our furry friends towards the top of the list.
Good for israel. There is so much animal cruelty it is disgraceful. It is great to see a country concerned with animal welfare!!!
Israel once again leads the way as a shining example of the best of humanity.
Great!! While many countries keep demonizing Israel here's a good lesson in humanity for this hypocritical Western world. Todah Israel! Interestingly figures like Bashevis Singer and other holocaust survivors have raised their voices against the horrible meat industry as a form of animal holocaust. What does the rest of the world need to realize that what we are doing to animals is terrible another human holocaust? So sad.
thank you Israel! you are the best!
I agree with Rex' mom…My boyfriend has been to Thailand several times and has told me that every hotel has a monkey tied to a chain to amuse the tourists. They tend to be obviously very dysfunctional and angry…yet it still amuses tourists ?
this is one of the best news ever!!! i really hope this became an examble for all the other countries! i love israel
This proves the bible came out of Isreal and Jesus out of the jewish people I know its the willof God to stop this horrid fur industry woulgnt it figure the first ban of fur there in the world in gods countryIsreal is way ahead of the game Im not even Jewish and these people writing in about palenstiens being oppressed over thier is just muslim propaganta to destroy Isreal and unforntuatly its been working and to addn the muslim religion cares less of nothing for animals and not much for thier own people thell kill em if they turn to another religion But here in the US everyone call your reps and senators cause the truth and lapeling act and ban on racoon dog fur is in the house now and going to the senate this makes them have to lapel all fur this isnt the best as banning all fur But its abig step to help stop the flo of fur from getting thru and people aware of the animals suffering LETS all call Isreal and give them our support on Ban And hope other coutries like US does it eventually
Thank You Jeff Mackey for posting this.
Good for Israel. Anyone think of the Uzi or the Galil? Great…ban fur. Keep pumping out guns and bombs…but ban fur. Good for you.
I'm proud to be israeli! love eretz israel! and to those people writing negative stuff about israel israel doesnt kill no children hamas does they throw rockets at israel and kill innocent kids AND DOGS in israel "palestinians" need to stop suicide bombing israel
If you are going to ban fur why not also ban leather? It's an animal product as well.
wow if this passes in Israel then I can only have respect for them for leading the way
I hope other countries will follow in the same foot steps of this wonderful and compassionate country of Isreal.
THANK YOU ISRAEL! This is good news to hear! You have my full support!
Yeah Israel! It is great that a country is finally taking action! It is amazing that countries like the United States still think fur is "attractive" and "luxurious". Why would someone want to wear a bloodied pelt? I hope countries will take Israel's lead and stop the bloody killing of animals.
Rexs mom I had watched a documentry and there is a specialty dish in india which involves goat fetus in a soup!!its absoutley disgusting!!I don't know but it doesn't sound very humane to me more like animals abortionist
The fact that India has 300 million vegetarians and major religions that oppose any form of cruelty against animals vindicates my comment. Ahimsa is a Indian creed for not causing any suffering to any being.
I am wondering what Brien on this site said about Thailand being an animal friendly nation. Unless they stopped Thais take baby elephants from their mothers and beats and tortures them to break their spirit so they can be used to pull lumber and other things. I hoped that country did stop torturning elephants and if they still do it it is still a very cruel country. Not too sure about India either. I think they do some cruel things to animals too.
What a wonderful thing that Israel is proposing to do. I just wish they would stop oppressing the Palestinian people as well.
This comes to no surprise that the wonderful country of Israel would do this. I find it a shame that my own country United States has not banned such killings for fur! Its an Outrage to say the least. The next time you see someone in fur you might mention to them how so many helpless animals were killed so they could enjoy "a luxury" item. Viva Israel. IsraelNeshama
Israel is one of the most educated countries on this planet per capita their people have the most degrees. This shows the aware and educated are the most caring compassionate and by being informed they know the suffering of animals is an important topic. We love Israel!
David. My sentiments exactly. I posted something similar but i suppose it wasn't approved by the blog owner.
Wow one of the only good things Israel has ever done. Congrats to them. Now if only they'd stop bombing groups of small children in Palestine…
I officialy love israel!!someone please give more information about the wonderful country and there humane lifestyle please!!america get with the program already!!
i love you israel
Way to go Israel!
Israel has long been one of the most humanitarian societies on the planet. Hunting is virtually nonexistent and their has always been a very strong proenvironment and wildlife recognition. Hopefully this ban will pass the Knesset and will be the beginning of a model for the world to emulate.
wow!.. I'm very impressed.. I do so hope it actually does go through.. and if it does.. surely a shining example to all the other countries.. who do and continue to support this ghastly trade.. by either producing fur ie. operating fur farms.. or importing fur pelts..or products derived form animal furs.. it's time for them to move out of the 'stoneage'
When this does happen this needs to make the news. Other countries need to wake up and realize WHY fur is being banned. People need to see that if one country is banning fur THERE IS A REASON FOR IT. From what I understand soon in Europe products tested on animals will be banned. This also needs to make worldwide news. We are a country that sticks our noses into everyone's business but yet turns a blind eye to the torture and cruelty of animals. If it wasn't for those whose hearts mind and souls cared about the animals our government obviously would not. I really pray for the sake of our animal companions other countries will follow in Israel's footsteps.
Israel is a far better country then is often portrayed. Civilized democratic and humane.
Israel is replete with vegetarians meatless eateries dog and cat shelters and equine sanctuaries. The antfur movement is strong. A great book is Judaism And Global Survival by Richard H. Schwartz. India and Israel are two of the most animal friendly nations and so is Thailand.
High five Israel! Why don't the rest of the "stubborn and ignorant" countries including my own USA wake the f….up and hop on board to end this Pathetic tradition of humans wearing fur. Because people who wear fur.. look like a bunch of morons!


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Precedents for THIS KIND OF THING are few and far between:
The editorial page of the Houston Chronicle expressed some buyer's remorse on Tuesday for endorsing Sen. Ted Cruz (R-TX) in last year's election.
In the editorial, the Chronicle lamented that Cruz did not take after his predecessor, fromer Sen. Kay Bailey Hutchison (R-TX)....
"When we endorsed Ted Cruz in last November's general election, we did so with many reservations and at least one specific recommendation – that he follow Hutchison's example in his conduct as a senator," the editorial read. "Obviously, he has not done so. Cruz has beenRead more


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Clever Lever Giga Craft Punch-Oval
Item #: 755967 | Model #: 271041 |
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About this itemA must have for every Scrapbooker and Crafter!
Good for personalizing greeting cards, place cards, bookmarks, scrapbooking pages and all paper crafts. The stainless steel metal blade is in a plastic body for added comfort and safety when you are working on your projects. The punched out shapes will vary in size according to the shapes but all shapes fit within a 3 circumference yet may not fully measure up to it.
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- [-] Other Available FormatsOur PriceNew & Used MarketplaceThe Fault in Our Stars (Paperback)
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More About The Fault In Our Stars by John GreenOverviewDespite the tumor-shrinking medical miracle that has bought her a few years, Hazel has never been anything but terminal, her final chapter inscribed upon diagnosis. But when a gorgeous plot twist named Augustus Waters suddenly appears at Cancer Kid Support Group, Hazel's story is about to be completely rewritten.
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Here's how RW members rated this race in the past (589 votes).
In short: Well done to everyone involved!In full: Despite only running an accidental shorter version, still really enjoyed this and didn't feel cheated in the slightest. Huge well done to the organisers and marshals for braving the horrid weather. A good race but you do need a bit of a sense of adventure / humour! Date of review: January 1, 2014
In short: Evening up the scoreIn full: Driving home, well more aquaplaning, I thought hmmmm two years ago I did the Olympic Version, today I did the well hmmm the Commonwealth Version and so I reckon overall somewhere in between than makes the full "usual" 10km. As ever a wonderful venue, superb organisation and a huge thank you to the marshalls and especially loved the snowman! Dr Rob as ever you are a fiend but thank you for a fun filled start to 2014. Happy New Year to all my fellow runners, the marshalls and to Dr Rob and his family.Date of review: January 1, 2014
In short: Brilliant way to bring in the New YearIn full: First time at the event. Loved the friendly atmosphere & fancy dress. Not a PB course but amazing views through driving rain & great crowd. Not worried about running the shorter course as I know what to expect next year & will put in a bit more training...... Left with a huge smile. Date of review: January 1, 2014
In short: Best race all year so far !In full: As if running up hills in the mud, rain and gales wasn't bad enough, they played bagpipes to us as well...!Great views (if the weather was better) but the fancy dress costumes were awesome. Hats off to the roman soldier, and the guys wearing kilts, smiles and not much else. Date of review: January 1, 2014
In short: Brillioant start to the yearIn full: Great race. Thanks to the organisers for persisting despite the weather and thanks to the marshals and spectators who were out there cheering us all on.Certainly blew the cobwebs away.Date of review: January 1, 2014
In short: Bagpipes, snowmen, steps, mud, rain, wind.In full: My first Knacker Cracker and I'm glad I braved the elements to stand dressed on Box Hill in the rain as a caveman. Dr Rob puts on very special events. I use the word 'special' here in the same way as I describe my two year old as a very special little boy, when he does things that are, well, special. Despite the rain, wind and mild hypothermia, I had a lot of fun and wasn't even too disappointed that the course was 40% shorter than advertised due to some missing signs (blown away in the wind?). In fact, I was quite happy to get back in my warm car and allow the heated seats to defrost my slightly broken body. Looking forward to doing it all over again next year. Date of review: January 1, 2014
In short: Fab race, interesting weatherIn full: Unfortunately I was one of the runners who took the wrong turn pretty early on in the race, so ran only about 4 miles. The weather was pretty tough, but a great spirit from all the runners and marshals. It was tough for the runner, but even tougher for the marshals - many thanks for your time chaps!A great race and I'm sure I'll be back for more next year - Thank you Dr RobDate of review: January 1, 2014
In short: Great way to start the yearIn full: What's great way to start the year. From the fantastic array of fancy dress on parade to the new nipper knacker race, Dr Rob and his band of merry Marshall's think of everything. It did seem to be a tad more slippery in places, even the crowd found it difficult to eat their cake in comfort!!! Thanks Dr Rob, same time and place next year?Date of review: January 1, 2014
In short: Muddy marvelousIn full: My fourth go at the KC and first in fancy dress. Excellent organisation as always, a hilly, slippery, muddy course and nice t-shirt and goodies (including soup) at the end. Thank you Dr Rob and the marshals, thoroughly enjoyableDate of review: January 11, 2013
In short: Hurts like hell but I keep coming back for moreIn full: The excellent organisation and atmosphere was no surprise but it was great to be blessed by glorious weather after all the wind and rain over Christmas. This was my 5th KC which seems to make me one of the veterans. Finished just outside of one hour so I guess that means I will need to come back and give it another crack. Thanks to Rob and all his team. Date of review: January 6, 2013
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Rogue Community College Gets $3 Million Grant
Rogue Community College is one of just 27 colleges in the country-and the only one in Oregon- to receive grant money for health care training programs. A projected 461 students will get training via the $3 million dollar grant, according to a press release from the school.
The money is coming via the U.S. Department of Labor. It will help train CNAs in acute, dementia, and restorative care; lab assistants; and physical therapy assistants. RCC will work in partnership with Lane Community College.
Among employment sectors in southern Oregon, the health care industry has typically experienced among the highest demand for workers. Southern Oregon's livability makes it a popular retirement destination for seniors.


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2 Responses to "Law and Social Cognition – Abstract"
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[…] understand science as applied to political and social phenomena. (One example is the application of cognitive science to law.) In the short-term though, the best thing we can do is simply to raise our standards. Issues like […]
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Flora Maria Vaccarino, MD
Harris Professor in the Child Study Center; Professor in the Department of Neuroscience
Research Interests
Central Nervous System Diseases; Mice, Inbred Strains; Mice, Transgenic; Neuroanatomy; Neurosciences; Patients; Regeneration; Developmental Biology; Living Donors; Psychiatry and Psychology
Research Organizations
Child Study Center: Family, Genetic and Molecular Research | Tic Disorder & Obsessive Compulsive Disorder Program | Vaccarino Lab
Interdepartmental Neuroscience Program
Kavli Institute for Neuroscience
Program in Neurodevelopment and Regeneration
Stem Cell Center, Yale: Stem Cell Genetics
WHRY Pilot Project Program Investigators
Research Summary
Stem cells are pluripotent cells that give rise to all tissues of the body, including neurons and glia of the central nervous system. Genome-scale complex regulatory processes unfold over time and space in the prenatal central nervous system to establish developmental programs that govern the differentiation of countless neuronal and glial cell types that populate the brain. Cell-intrinsic, species-specific genetic blueprints as well as cell-to-cell contacts and signaling systems govern these complex regulatory processes and render them more robust to perturbations. We hypothesize that slight deviations from typical programs of differentiation and patterning of neural stem cells predispose to disorders such as autism, Tourette syndrome, and schizophrenia. Induced pluripotent cells (iPSC) derived from living individuals and differentiated into telencephalic organoids recapitulate forebrain development in a dish, allowing us to examine typical and atypical development in patients with neuropsychiatric disorders and the underlying gene regulatory processes. Specifically we study the impact of noncoding RNAs, histone modifications, enhancer activity, and somatic mutations on typical and atypical brain development in human brain organoid culture and, whenever possible, in vivo.
Specialized Terms: Neural stem cells; Cerebral cortex; Neuronal progenitors; Postmortem human brain; Induced pluripotent stem cells; somatic mosaicism, enhancer activity, gene expression, telencephalic organoids.
Extensive Research Description
The Vaccarino laboratory has elucidated crucial mechanisms that regulate neural stem cell self-renewal, survival and differentiation. The lab has been examining conserved mechanisms of forebrain development using mouse models, and human-specific mechanisms by examining human stem and progenitor cells. Using induced pluripotent cells (iPSC) derived from living individuals the Vaccarino group is now examining how human stem cell differentiation varies across different genetic backgrounds, genders, and clinical phenotypes.
In the 1990's Vaccarino and colleagues reported that an extracellular protein called Basic Fibroblast Growth Factor 2 (FGF2) increases the number of progenitors for excitatory cortical neurons in vitro (Vaccarino et al., 1995) and that a single microinjection of FGF2 into the cerebral ventricles of rat embryos doubled the number of excitatory pyramidal neurons generated during cortical development, producing an increase in cortical surface area (Vaccarino et al., 1999). Cortical pyramidal neurons form the primary scaffold of the cortex, and this was the first evidence that a single factor can elicit a permanent increase in pyramidal neuron number and cerebral cortical size in a mammalian species. Conversely, using knockout mice, Vaccarino and colleagues demonstrated that the Fgf2 gene product is essential for the generation of the species-specified number of excitatory neurons in the cerebral cortex by increasing cell proliferation in the cortical neuroepithelium (Vaccarino et al., 1999; Raballo et al., 2000; Korada et al., 2002). Subsequent work demonstrated that FGF receptors are essential for normal telencephalic development in region-specific fashion. The disruption of the Fgfr1 gene is sufficient to thwart cell proliferation within the hippocampal primordium, causing lifelong hippocampal atrophy (Ohkubo et al., 2004). However, abolishing the function of single FGF receptors causes minor abnormalities in cortex because all FGF receptors contribute redundantly to cortical development. However, the double knockout of Fgfr1 and Fgfr2 causes prefrontal cortex volume loss with fewer pyramidal cells (Stevens et al, 2010), and the combined knockout of Fgfr1, Fgfr2 and Fgfr3 in early neurogenesis depletes the cortical stem cell pool globally, resulting in premature ending of neurogenesis and decreased cortical surface area (Rash et al, 2011). Conversely, a microinjection of FGF2 in the lateral ventricles at pre-neurogenic stages of cortical development generates a massive enlargement of frontal cortical surface and the appearance of gyrus-like convolutions in stereotypic bilateral locations (Rash et al, 2013).
In summary, our studies have shown that FGFs establish the primary structure and the surface area of the cerebral cortex by promoting the self-renewal of neural stem cells and the differentiation of projection neurons from neuroepithelial precursors. We are currently studying the molecular mechanisms whereby FGF signaling affects the development of neocortical structure and size.
The lab has been redefining the roles of astroglial cells—extremely diverse cellular elements that evolve from a primary role of neural progenitors during embryonic development, to essential partners in neuronal migration, maturation, axon guidance. These cells have essential metabolic function in the adult brain and retain ability to divide and act as precursors. To further study the role of astroglial stem/progenitor cells in regenerative processes, the lab has generated the GFAP-CreERT2 transgenic line, in which the Cre recombinase can be transiently induced by a tamoxifen injection in GFAP+ astroglial cells (Ganat et al, 2006). By marking GFAP+ astroglial cells via recombination of genetic reporter we found that astrocytes can produce neurons in the immature brain, a process that is enhanced by hypoxic injury (Fagel et al., 2006, and Fagel et al, 2009; Bi et al, 2011) and dependent in part upon FGF receptor function (Fagel et al, 2009; Stevens et al, 2102). Indeed, Fgf ligands also play roles in different epochs of postnatal and adult life. FGF receptor functioning is required in astroglia to indirectly promote the maturation of inhibitory interneurons during the early postnatal development of the cerebral cortex (Müller Smith et al, 2014). Induced loss of FGF signaling only in postnatal astrocytes generates stereotypic locomotor hyperactivity and learning and memory defects that correlate with deficit in specific cell populations in the postnatal brain (Müller Smith et al, 2008, Stevens et al, 2012).
Another theme that the Vaccarino lab has been pursuing is whether an excitatory/inhibitory neuron imbalance in specific forebrain systems due to disparate etiologies (i.e., gene mutations; prenatal factors; environmental noxae) may predispose to neuropsychiatric disorders such as autism and Tourette syndrome.
For example, we have shown that individuals with Tourette's syndrome (TS) have losses of Parvalbumin and cholinergic interneurons in specific regions of the striatum. TS is a developmental disorder of childhood characterized by motor and vocal tics. We demonstrated a large decrease in three classes of interneurons in the striatum of TS: Parvalbumin+; NOS+/NPY+/SST+; and cholinergic (Kalanithi et al, 2005; Kataoka et al, 2010). RNA sequencing of the postmortem striatum of deceased TS individuals revealed decreased expression of 308 genes, encompassing transcripts related to these three classes of interneurons, and decreased inhibitory neurotransmission in general. The study also revealed an up-regulation of 822 genes representing inflammatory response- and immune system-related genes (Lennington et al., 2014). The hypothesis is that altered postnatal maturation/survival of subsets of inhibitory neurons in cortico-basal ganglia circuits causes specific alterations in synchronous neuronal firing that may model disorders of the TS spectrum.
Current studies aim at analyzing genetic and epigenetic differences in striatal and cortical tissue and within isolated cell types between TS and matched controls.
A deficit in inhibitory neurons has been found in the cortex of schizophrenic patients, and it has been postulated to occur in autism spectrum disorders (ASD). To model disorders of cortical development in a human system, the lab has recently adopted the induced pluripotent stem cell (iPSC) model and has developed a new way to derive cortical organoids from iPSCs as a window into normal and abnormal neuronal development (Mariani et al, 2012). Over the last several years Vaccarino and colleagues have derived hundreds of iPSC lines from patients with developmental disorders. They established a new protocol for converting iPSCs into brain organoids that reflect the human cerebral cortex at mid-fetal stages of development, which contain the main classes of excitatory cortical neurons and inhibitory interneurons. Using this tool, Vaccarino and colleagues have recently contributed fundamental work on neurodevelopmental alterations in severe, idiopathic ASD. Transcriptome and cell fate studies in organoids from ASD affected individuals as compared to unaffected family members indicated alterations in cell proliferation, overproduction of synapses and a striking increase in GABAergic neurons and their precursors, showing that ASD derived organoids have excess rather than defect in inhibitory GABAergic neurons (Mariani, Coppola et al, Cell, 2015). The work has also revealed an important role of the transcription factor FOXG1 in the overproduction of GABAegic precursor cells (Mariani, Coppola et al, Cell, 2015).
Ongoing studies integrate genomes, transcriptomes and cellular phenotypes to explore the etiology of autism and other neurodevelopmental alterations. As part of the PsychENCODE collaborative multi-site project, the lab will generate a genome-scale catalog of coding and noncoding RNAs and functional DNA elements in iPSC-derived organoids and human brain specimens of the same genetic background. Our object within the PsychENCODE is to verify to what extent the iPSC-derived organoids reflect true human brain development.
Selected Publications
- The PsychENCODE Consortium, Akbarian, S., Liu, C., Knowles, J.A., Vaccarino, F.M., Farnham, P., Crawford, G.E., Jaffe, A.E., Pinto, D., Dracheva, S., Geschwind, D.H., Mill, J., Nairn, A.C., Abyzov, A., Pochareddy, S., Prabhakar, S., Weissman, S., Sullivan, P.F., State, M.W., Weng, Z., Peters, M.A., White, K., Gerstein, M.B., Senthil, G., Lehner, T., Sklar, P., Sestan, N.: The PsychENCODE Project. Nature Neuroscience, accepted for publication.
- Patriarchi, T., Amabile, S., Frullanti, E., Landucci, E., Lo Rizzo, C., Ariani, F., Costa, M., Olimpico, F., Hell, J. W., Vaccarino, F.M., Renieri, A., Meloni, I.: Imbalance of Excitatory/Inhibitory Synaptic Protein Expression in iPSC-derived Neurons from FOXG1+/- Patients and in Foxg1+/- Mice. European Journal of Human Genetics, in press.
- Salmaso, N., Dominguez, M., Kravitz, J., Komitova, M., Vaccarino, F.M. & Schwartz, M.L.: Contribution of maternal oxygenic state to the effects of chronic postnatal hypoxia on mouse body and brain development. Neurosci. Lett, in press.
- Frullanti, E., Amabile, S., Lolli, M.G., Bartolini, A., Livide, G., Landucci, E., Mari, F., Vaccarino, F.M., Ariani, F., Massimino, L., Renieri, A., Meloni, I.: Altered expression of neuropeptides in FoxG1-null heterozygous mutant mice. European Journal of Human Genetics, in press.
- Leckman, J.F., Vaccarino, F.M. Editorial Commentary: What Does Immunology have to do with Brain Development and Neuropsychiatric Disorders? Brain Res, in press. Special Issue "Neuroimmunology in Health And Disease."
- Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., Gerstein, M., Grigorenko, E., Chawarska, K., Pelphrey, K., Howe, J., Vaccarino, F.M.: FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell. (2015) 162(2):375-390.
- Stevens, H. E., and Vaccarino, F.M.: How animal models inform child and adolescent psychiatry. Journal of the American Academy of Child and Adolescent Psychiatry (2015) 54(5):352-359.
- Ardhanareeswaran, K., Coppola, G., and Vaccarino, F.M.: The Use of Stem Cells to Study Autism Spectrum Disorder. The Yale Journal of Biology and Medicine (2015) 88(1):5-16.
- Xu, M., Kobets, A., Du, J.-C., Lennington, J.B., Li, L., Banasr, M., Duman, R.S., Vaccarino, F.M., DiLeone, R., Pittenger, C.: Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc. Natl. Acad. Sci. USA (2015) 112(3):893-8.
- Transcriptome Analysis of the Human Striatum in Tourette Syndrome. JB Lennington, G Coppola, Y Kataoka-Sasaki, TV Fernandez, D Palejev, Y Li, A Huttner, M Pletikos, N Sestan, JF Leckman, FM Vaccarino (2014). Biol Psychiatry.
- Lennington, J.B., Bloch, M.H., Scahill, L.D., Szuhay, D., Lombroso, P.J., and Vaccarino, F.M.: "Tourette Syndrome". In: "Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease", Elsevier (2014).
- Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding. JG Kim, S Suyama, M Koch, S Jin, P Argente-Arizon, J Argente, ZW Liu, MR Zimmer, JK Jeong, K Szigeti-Buck, Y Gao, C Garcia-Caceres, CX Yi, N Salmaso, FM Vaccarino, J Chowen, S Diano, MO Dietrich, MH Tschöp, TL Horvath (2014). Nat Neurosci 17: 908-10.
- Neurogenesis and Maturation in Neonatal Brain Injury. Salmaso, N., Tomasi, S. and Vaccarino, F.M. In Advances in Neonatal Neurology, edited by P. Ballabh and S. Back, Elsevier (2014).
- Neurobiology of premature brain injury. N Salmaso, B Jablonska, J Scafidi, FM Vaccarino, V Gallo (2014). Nat Neurosci 17: 341-6.
- Fgfr1 inactivation in the mouse telencephalon results in impaired maturation of interneurons expressing parvalbumin. KM Smith, ME Maragnoli, PM Phull, KM Tran, L Choubey, FM Vaccarino (2014). PLoS One 9: e103696.
- Hypoxia-induced developmental delays of inhibitory interneurons are reversed by environmental enrichment in the postnatal mouse forebrain. M Komitova, D Xenos, N Salmaso, KM Tran, T Brand, ML Schwartz, L Ment, FM Vaccarino (2013). J Neurosci 33: 13375-87.M Komitova, D Xenos, N Salmaso, KM Tran, T Brand, ML Schwartz, L Ment, FM Vaccarino (2013). J Neurosci 33: 13375-87.
- Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration. Y Zhang, VP Schulz, BD Reed, Z Wang, X Pan, J Mariani, G Euskirchen, MP Snyder, FM Vaccarino, N Ivanova, SM Weissman, AM Szekely (2013). Proc Natl Acad Sci U S A 110: 12361-6.
- Cortical gyrification induced by fibroblast growth factor 2 in the mouse brain. BG Rash, S Tomasi, HD Lim, CY Suh, FM Vaccarino (2013). J Neurosci 33: 10802-14.
- Prenatal stress delays inhibitory neuron progenitor migration in the developing neocortex. HE Stevens, T Su, Y Yanagawa, FM Vaccarino (2013). Psychoneuroendocrinology 38: 509-21.
- Age-related changes of gene expression in the neocortex: preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas. OY Naumova, D Palejev, NV Vlasova, M Lee, SY Rychkov, ON Babich, F M Vaccarino, EL Grigorenko (2012). Dev Psychopathol 24: 1427-42.
- Abyzov, A., Mariani, J., Palejev, D., Zhang, Y., Haney, M.S., Tomasini, L., Ferrandino, A., Rosenberg Belmaker, L., Szekely, A., Wilson, M., Kocabas, A., Calixto, N.E., Grigorenko, E.L., Huttner, A., Chawarska, K., Weissman, S., Eckehart Urban, A., Gerstein, M, FM Vaccarino Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. (2012) Nature 492(7429):438-42.
- Mariani, J., Simonini, M.V., Palejev, D., Tomasini, L., Coppola, G., Szekely, A., Horvath, T., & Vaccarino, F.M. (2012). Modeling human cortical development in vitro using induced pluripotent stem cells. Proceedings of the National Academy for Sciences USA, 109(31), 12770-12775.
- Stevens, H.E., Mariani, J., Coppola, G., & Vaccarino, F.M. (in press). Neurobiology meets genomic science: The promise of human induced pluripotent stem cells. In Grigorenko, E. L., & Cicchetti, D. (Eds.), The contribution of genetic/genomic sciences to developmental psychopathology [Special Issue], Development and Psychopathology, 24(4), 1443-1451.
- Rash, B.G., Lim, H.D., Breunig, J.J., and Vaccarino, F.M.: FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J Neurosci, 31: 15604-17, 2011.
- Vaccarino, F.M., Urban, A.E., Stevens, H.E., Szekely, A., Abyzov, A.,Grigorenko, E.L., Gerstein, M.,Weissman, S.: Annual Research Review: The promise of stem cell research for neuropsychiatric disorders. J Child Psychol Psychiatry, Ed. 2011/01/06, Jan 4.
- Silbereis, J., Heintz, T., Taylor, M.M., Ganat, Y.M., Ment, L.M., Bordey, A., Vaccarino, F.M.: Astroglial cells in the external granular layer are precursors of cerebellar granule neurons in neonates. Molecular Cell. Neurosci. (2010) 44:362-373.
- Kataoka, Y., Kalanithi, P.S.A., Grantz, H., Schwartz, M.L., Saper, C., Leckman, J.F., Vaccarino, F.M.: Decreased Number of Parvalbumin and Cholinergic Interneurons in the Striatum of Individuals with Tourette Syndrome. J. Comp. Neurol. (2010) 518:277-291. Epub 9/16/2009.
- Stevens, H. E., Smith, K. M. , Maragnoli, M. E. , Fagel, D., Borok, E., Shanabrough, M., Horvath, T. L., Vaccarino, F. M.: Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J. Neurosci. (2010) 30:5590-5602.
- Vaccarino, F. M., Smith, K.M.: Increased Brain Size in Autism-What it Will Take to Solve a Mystery. Biological Psychiatry 66:313-315, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19643218?dopt=Citation
- Vaccarino, F. M., Smith, K.M., Stevens, H.: Regulation of cerebral cortical size and neuron number by Fibroblast Growth Factors: Implication for autism. Journal of Autism and Developmental Disorders, 39:511-20,2009. http://www.springerlink.com/content/ym775r15gv111658/fulltext.html
- Silbereis, J, Cheng, E, Ganat, YM, Ment, LM, Vaccarino, FM: Precursors with GFAP promoter activity transiently generate GABA interneurons in the postnatal cerebellum. Stem Cells 27:1152-1163, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19418461?dopt=Citation
- Fagel, D.M., Silbereis, J., Ohkubo, Y., Ganat, Y., Ment, L.R., Vaccarino, F.M.: Fgfr-1 Is Required For Cortical Regeneration and Repair following Perinatal Hypoxia. Journal of Neuroscience (2009) 29(4):1202-1211. http://www.ncbi.nlm.nih.gov/pubmed/19176828?dopt=Citation
- Smith, KM, Fagel, DM, Stevens, HE, Rabenstein, RL, Maragnoli, ME, Ohkubo, Y, Picciotto, MR, Schwartz, ML, Vaccarino, FM: Deficiency in inhibitory cortical interneurons associates with hyperactivity in Fgfr1 mutant mice. Biological Psychiatry, 2008, 63:953-962. http://www.ncbi.nlm.nih.gov/pubmed/17988653?dopt=Citation
- Ganat, Y.M., et al. (2006). Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo. J. Neurosci. 26:8609-8621. http://www.ncbi.nlm.nih.gov/pubmed/16914687?dopt=Citation
- Fagel DM, Ganat Y, Silbereis J, Ebbitt T, Stewart W, Zhang H, et al. Cortical neurogenesis enhanced by chronic perinatal hypoxia. Exp Neurol 2006199(1):77-91. http://www.ncbi.nlm.nih.gov/pubmed/15916762?dopt=Citation
- Smith, K.M., et al. (2006). Midline radial glia translocation and corpus callosum formation require FGF signaling. Nat. Neurosci. 9:787-797. http://www.ncbi.nlm.nih.gov/pubmed/16715082?dopt=Citation
- Kalanithi PS, Zheng W, Kataoka Y, DiFiglia M, Grantz H, Saper CB, et al. Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proceedings of the National Academy of Sciences U S A 2005;102(37):13307-12. http://www.ncbi.nlm.nih.gov/pubmed/16131542?dopt=Citation
- Ohkubo, Y, Uchida, AO, Shin, D, Partanen, J. and Vaccarino, FM: Fibroblast Growth Factor Receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse. J Neurosci, 24: 6057-6069, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15240797?dopt=Citation
- Zheng, W, Nowakowski, R, and Vaccarino, FM: Fgf2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Developmental Neurosci, 26:181-196, 2004.
- Shin, D, Korada, S, Raballo, R, Shashikant, CS, Simeone, A, Taylor, J, and Vaccarino, FM: Loss of Glutamatergic pyramidal neurons in frontal and temporal cortex due to attenuation of FGFR1 signaling is associated with spontaneous hyperactivity in mice. J Neurosci, 24:2247-2258, 2004.
- Ganat, Y, Soni S, Chacon, M, Schwartz, ML and Vaccarino, FM: Chronic hypoxia upregulates Fibroblast Growth Factor (Fgf) ligands in the perinatal brain and induces Fgf-responsive radial glial cells in the subependymal zone. Neuroscience,112:977-991, 2002.
- Korada, S, Zheng, W, Basilico, C, Schwartz, ML and Vaccarino, FM: Fgf2 is necessary for the growth of glutamate projection neurons in the anterior neocortex. J Neurosci, 22:863-875, 2002.
- Raballo, R, Rhee, J, Lyn-Cook, R, Leckman, JF, Schwartz, M.,Vaccarino, FM: Basic Fibroblast Growth Factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex J Neurosci, 20:5012-5023, 2000. http://www.ncbi.nlm.nih.gov/pubmed/10864959?dopt=Citation
- Vaccarino, FM, Schwartz, ML, Raballo, R, Nilsen, J, Rhee, J, Zhou, M, Doetschman, T, Coffin, JD, Wyland, J, Hung, Y-T: Changes in cerebral cortex size are governed by Fibroblast Growth Factor during embryogenesis. Nature Neurosci, 3: 246-253, 1999. http://www.ncbi.nlm.nih.gov/pubmed/10195217?dopt=Citation