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Dos galgos grandes y fieles abandonados en el parque de al lado de mi casa... que asco me dan las personas que hacen esoIl y a environ 16 heuresvia web from Las Palmas de Gran Canaria, Las Palmas
Though not a fan of romance novels, I have enjoyed this short holiday-themed book. Gabby, the out-spoken, forceful matriarch of her family gathers her adult children, relatives, friends, and almost everyone she knows for her Christmas wedding. She discusses her wedding plans in a series of video messages without identifying the groom. Emotional outbursts, unconventional wisdom, and smiley smiles ensue. This warm, amusing plot line is as far from reality as it can be. Will it become a Lifetime movie some day?
If you are in the mood for over-the-top characterization and story, this feel-good book may be the one for you. View all my reviews
iFresh Rechargable External Battery from SWE, Inc. is the Must Have Accessory for iPhone, iPod and iPod Touch? (December 27, 2011)
Tustin, CA (PRWEB) December 27, 2011
SWE, Inc. announces the must have accessory for anyone who received an iPhone or iTouch for Christmas the iFresh rechargeable external battery.
Apple approved for iPhone, iPod and iPod touch, iFresh plugs directly into the 30-pin connector on the device and provides instant power while recharging the device battery. iFresh features a powerful 2200 mAh battery - the most powerful available on any comparable product - and can bring a device to full battery charge in less than two hours. The product works on iPod, iPod touch, iPhone 3, iPhone 3GS, iPhone 4 and iPhone 4S as well as iPad devices. A patented retractor clip makes it easy to remove iFresh from the unit when it has provided adequate power.
iFresh is lightweight at just three ounces so it is easy to carry right in a shirt or jacket pocket in order to provide power to your Apple device anytime it is needed. A LED indicator on iFresh shows how much power is left in the unit. iFresh is easily recharged through an included retractable USB cable that connects to any Mac or PC, as well as any car charger that has a USB port. iFresh can be drained and recharged 500 times. It is the ideal product for any iPhone or iTouch user who needs to be able to keep connected while on the go without having to worry about finding a power source where they can recharge their device.
iFresh is available for just $59.95 online with free shipping at the SWE, Inc. official website, http://www.shopwithease.com,.
ABOUT SWE, INC.
Located in Tustin, CA SWE, Inc. is a leading distributor of specialty electronic, home, fashion, beauty and As Seen on TV product including the AutoChron programmable wall switch timer, Comfy Puppy Shoe & Boot Stretchers and Porta-Jump Portable Emergency Jump Starter. Many of SWEs products have been featured on both HSN and QVC, as well as carried by retailers including Target, Lowes, Frys and Costco.com.
iPhone, iPod classic, iPod nano, iPod shuffle, and iPod touch are trademarks of Apple Inc., registered in the U.S. and other countries. Made for iPod and iPhone means that an electronic accessory has been designed to connect specifically to iPod and iPhone, and has been certified by the developer to meet Apple performance standards. Apple is not responsible for the operation of the device or its compliance with safety and regulatory standards.
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Read the full story at http://www.prweb.com/releases/2011/12/prweb9064150.htm.
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She of the famed Rachel hairdo ? which the actress later described as the "ugliest haircut (she'd) ever seen" ? explained why she cut her hair into a chic, shoulder-length bob right smack in the middle of her "Just Go With It" promotion tour last February.
PHOTOS: Stars' Bad Hair Days
"The real reason I cut my hair? My real hair was getting thinned out again from all the extensions," the 42-year-old "Horrible Bosses" actress said matter-of-factly in the January issue of In Style. "It was starting to look fake."
Story: Poll: Americans want to dine with Aniston, Pitt
On hair chameleons like Katy Perry and Rihanna, such a change would have been no big deal, but Jen's gorgeous, shiny mane hadn't been seen a major transformation in years.
PHOTOS: Fashion Spotlight: Jennifer Aniston
More recently, Jen ? who's living in New York City with beau Justin Theroux--has been spotted growing out her sunny blond layered locks.
? 2011 E! Entertainment Television, Inc. All Rights Reserved.
A former writer for the PhoneDog website is being sued by the company not for leaving it, but for leaving with PhoneDog's name as part of his Twitter handle, resulting in a lawsuit and raising the question of who really owns a Twitter name? And is it worth the kind of damages PhoneDog is seeking?
Noah Kravitz is facing the suit by Phone Dog Media, which says that when Kravitz left the company in October 2010, he took with him the Twitter name "Phonedog_Noah" (tied to his personal email) ? and 17,000 followers. The company is seeking damages of $340,000 ? $2.50 a month for every follower for the eight months Kravitz used "Phonedog_Noah" (until he was served with the suit).? He now goes by "noahkravitz."
Kravitz, who has gone public to talk about the issue, said when he left, PhoneDog, which covers cellphone news, said he could continue with the "Phonedog_Noah" account in exchange for tweeting for the company "from time to time."
Phone Dog Media has kept mum ? and definitely not tweeted ? about the lawsuit, but did issue this statement to the New York Times, which recently wrote about the case: ?The costs and resources invested by PhoneDog Media into growing its followers, fans and general brand awareness through social media are substantial and are considered property of PhoneDog Media L.L.C. We intend to aggressively protect our customer lists and confidential information, intellectual property, trademark and brands.?
Kravitz, who now writes for TechnoBuffalo, said he's not sure how PhoneDog came up with the monetary formula it used in seeking damages for the total of $340,000.
"If you took their valuation and if you applied it to the Twitter accounts of somebody like Lady Gaga or Shaq, you'd have the gross domestic product of more than one nation on earth per month," he recently said in a CNN interview.
The case, attorney Henry J. Cittone, a specialist in intellectual property disputes, told the Times, will "establish precedent in the online world, as it relates to ownership of social media accounts."
In the meantime, publicity is bringing Kravitz many other Twitter followers; as of Tuesday, he had more than 23,700 of them.
Related stories:
Check out Technolog, Gadgetbox, Digital Life and In-Game on?Facebook,?and on Twitter, follow Suzanne Choney.
In about two months, students will pour into the sunlit hallways of Richmond's new, $18.5 million Ford Elementary School for the first time.
It has been a long 60 months coming, a process that began with teachers, parents and other members of the community offering their vision of what an urban school should look and feel like.
What emerged was a clear departure from the stereotypical, rectangular inner-city school with a chain-linked, industrial feel.
In this West Contra Costa community, the adults wanted to send a clear message to the kids: "You are important," said Associate Superintendent Bill Fay.
Richmond's newest school is a stuccoed two-story building marked by occasional arches, sloping tiled roofs, a windowed tower, and earthy yellow, orange and blue paint.
Inside, classrooms are brightly colored, with varying geometric patterns of linoleum on the floors. Shredded denim is hidden inside the walls, a nontoxic form of insulation that keeps rooms at an even temperature and quiet.
Stylish, elegant
Exposed ducts, stylish lighting fixtures, wood-plank ceilings and loftlike views from the second floor give the school a hip, elegant feel.
"I wanted it to be nice," architect Sally Swanson said with a shrug as she toured the school's halls while workers put the finishing touches on the site. "I wanted them to feel like this is home. I wanted it to be fun."
Buildings are just the brick-and-mortar part of a public education, but they set the tone for the children who walk through the door to learn, district officials said. The graffiti-covered walls of the 60-year-old school it replaces - along with nonworking water fountains, broken bathrooms, old technology, bad lighting and dull colors - send the wrong message.
Even with the fancy styling and an environmentally conscious drainage system that filters out pollutants, the project is about $5 million dollars under budget - thanks to competitive bidding among contractors looking for work in a sluggish economy, Swanson said.
Rebuilding program
Brand-new schools are rare in most other urban school districts; facility funds are more often used to modernize and upgrade existing sites.
The Ford Elementary School project is one of several schools in West Contra Costa that have been or will be completely rebuilt, each with their own character designed to serve the students' needs. Nearly all the district's 57 schools are getting some kind of makeover made possible by more than $1 billion in facility upgrades funded by five voter-approved bonds and state funding since 1998.
Some of the new sites have incorporated things like dental clinics, recognizing that many students don't have access to such medical services and that tooth pain means kids can't learn.
Swanson designed a building at Ford Elementary to address the needs of the school's 400 students, who are predominantly Latino. Clean air flows from vents near the floor, up through the room and out other vents near the ceiling. The system is meant to help alleviate the asthma that so often plagues inner-city kids.
Other highlights
Less visible features include nearly 60 security cameras, three places to lock down the school in emergencies, a gated periphery, motion detectors to turn on lights and key cards for entry. Bikes will be locked up during the day.
Other features include a room for parents and an outdoor placita, or plaza, to accommodate the moms who often spend a good part of the day at the school.
There is an outdoor education area and a large garden.
Classrooms will have video transceivers, televisions and media carts, allowing teachers to broadcast lessons, plays or projects across the school.
"A facility really should, in the best of all worlds, be an enhancement to our core mission of education," said Fay, the associate superintendent. "We are building top-of-the-line facilities for our communities."
This article appeared on page C - 1 of the San?Francisco?Chronicle
By Megan Poinski (Megan@MarylandReporter.com) and Len Lazarick (Len@MarylandReporter.com)
(December 23, 2011) -- Racial politics and concerns about community cohesion dominated a three-hour hearing Thursday as scores of people from across Maryland came to Annapolis to condemn, offer suggestions and even praise the new legislative district map drawn by Gov. Martin O?Malley?s Redistricting Advisory Committee.
The map, which was the product of census data and comments from a dozen hearings across the state this summer, was first unveiled online last Friday. O?Malley said he had the hearing to give the people a chance to see and comment on it before he sends it to the General Assembly next month.
O?Malley listened to all of the testimony and said no one would likely say that the new map was better than the old one, but it was made necessary by shifting populations found in last year?s census. He said he would try to address as many concerns as possible before finalizing the map and presenting it to the legislature.
?We are all in this together, and there is no change in one district that does not affect another district, one neighborhood that does not affect another,? O?Malley said.
Afterward he told reporters, ?Of course, I?m open to making tweaks. ? This is a real process.? But ?I don?t expect it to change very much.?
Senate President Mike Miller, a member of the redistricting committee, promised that once O?Malley revises the map and passes it along to the General Assembly next month, there would be another public hearing on the proposed district lines.
More minority districts demanded
In sometimes emotionally charged testimony, committee members heard several African-Americans asking for more districts where they would be in the majority.
Carletta Fellows of the Fannie Lou Hamer political action committee ? which is currently challenging the congressional redistricting map in federal court ? did not mince words when she talked about the map. She called it ?a miscarriage of justice? and should show ?greater sensitivity to the black and brown community.?
Del. Tiffany Alston, D-Prince George?s County, said that looking at the demographics of the state, there should be 14 senatorial districts with a majority of black residents. She said she would not be happy with a map that doesn?t give African-Americans the appropriate voting strength in the state.
?As a Democrat, I find this map to be a slap in the face to black Democrats,? she said.
Sen. Anthony Muse, D-Prince George?s, said that Maryland?s non-minority white population declined to nearly 55% ? yet the proposed map seems to over represent whites.
Del. Aisha Braveboy, D-Prince George?s County, chair of the redistricting committee of the Legislative Black Caucus, pointed out some problems she saw in districts in her county. Nearly 86% of the population in the 24th District ? which includes Glenarden, Seat Pleasant and Fairmount Heights ? is black. Meanwhile, there are other districts that could be drawn with stronger black majorities, but aren?t.
Sen. Delores Kelley, D-Baltimore County, said the proposed map moves her own District 10 in western Baltimore County into more rural areas with fewer African-Americans, in order to create a district shared with Baltimore City.
Elbridge James, speaking to the committee on behalf of the NAACP, asked O?Malley and his committee to take the comments about minorities into consideration.
?If these issues are not addressed, the participation opportunities of African-Americans will be severely limited, and this will stand for 10 years,? James said, until the next census.
Andy Carruthers, a white Prince George?s resident, took an opposite view, saying that looking so closely at race to draw district lines was ?terribly harmful.? Though some people may vote solely based on a candidate?s race, that is not the way it always happens.
?Have we learned so little from the last presidential election?? Carruthers asked.
Keep communities together
Several residents of smaller communities, startled to learn that the proposed district lines bisected their neighborhoods, pleaded with committee members to keep their hometowns intact.
Lake Arbor, a small community in Prince George?s County near FedEX Field, is proposed to be split between the Districts 24 and 25. Angry residents met with Braveboy and Del. Dereck Davis to ask for their hometown to stay in one district. Braveboy presented the committee with a redrawn map that would accomplish this, and several long-time residents testified before the committee.
Lake Arbor resident Brian Austin said he is sure there was no malice intended when the map divided the community, but it upset him all the same.
?Division of an otherwise ideal environment makes no sense,? he said. ?Division of a community that works together makes no sense.?
Eric Rockel, president of the Greater Timonium Community Council, was upset that the map did not put Timonium back together. The current districts split the Baltimore County community along I-83. While it is not an ideal situation, Rockel said that using the highway as a boundary makes sense.
The proposed map, however, still bisects Timonium ? but no longer uses the highway as a boundary.
?My emotions went from disappointment to disillusionment to cynicism when I read the governor?s press release,? Rockel said. ?He said he kept communities together, but not Timonium.?
Residents from Woodmore and Lanham-Seabrook in Prince George?s County had similar complaints.
Republican Dels. Cathy Vitale and Tony McConkey asked that Severna Park in Anne Arundel County not be split in three districts as proposed.
Some were satisfied
Though there were fewer people who said they were pleased with the map as drawn, some did come out to the hearing solely to praise the work of the committee.
Howard Gorrell, who attended all 12 statewide hearings of the redistricting committee, said he liked the way that district lines were drawn in Western Maryland, in keeping with testimony at the hearings.
Del. Ana Sol Gutierrez, D-Montgomery County, had some negative things to say about the plan, but was thankful that the committee paid attention to the emerging Latino population with a possible single-member majority district in Montgomery County.
Charles Berman of Derwood said that the last 10 years ? when illogical district lines split up his hometown ? were not good. However, Derwood is in a single district again on the proposed map.
Green Bay - Mike McCarthy's Monday press conference gets under way at 3 p.m.
Stay here for all the highlights.
If you're on a mobile device, go here.
Here's a recap: McCarthy reported that several players who were hurt may return to practice this week and could play.
WR Greg Jennings may practice on Wednesday. Same with OT Bryan Bulaga. McCarthy's hope is to play Chad Clifton against the Lions to see whether he can help in the playoffs.
DE Ryan Pickett is taking some tests today to see if he can return to the practice field. RB James Starks will be hard-pressed to practice on Wednesday, which means he's probably doubtful.
McCarthy said he is going for 15-1. He wants to sweep the division. He didn't guarantee that he wouldn't rest anybody, but his message is that the Packers aren't going to let up against the Lions Sunday.
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Techmeme Berkeley Explains Why Google Trumps Microsoft (Caleb Garling/Wired Enterprise): Caleb Garling / Wired... bit.ly/vC8BlIIl y a environ 8 heuresvia twitterfeed
1.Double-click the new icon on the desktop labeled R228571.exe. 2.The Self-Extracting window appears and prompts you to extract or unzip to C:\DELL\DRIVERS\R228571. Write down this path so the executable (I.e. Setup.exe) file can be found later. 3.The Self-Extractor window appears. 4.Click OK. 5.After completing the file extraction, if the Self-Extractor window is still open, close it. 6.Click the Start button and then click Run. 7.Type C:\DELL\DRIVERS\R228571 in the Open textbox and then click OK. 8.Follow the on-screen installation instructions.
It is highly recommended to always use the most recent driver version available.
Do not forget to check with our site as often as possible in order to stay updated on the latest drivers, software and games.
Try to set a system restore point before installing a device driver. This will help if you installed a wrong driver. Problems can arise when your hardware device is too old or not supported any longer.
Twitter / Marshano: mijn google chrome, mozill ...mijn google chrome, mozilla, internet, paint, skype, tweetdeck en 'mijn bestanden' loopt vast, maar msn neitIl y a environ 2 heuresvia web
Choose from two great hotels: Ocean Breeze Riviera Maya Hotel at Playa del Carmen or the Sea Garden Hotel in Nuevo Vallarta.
Ocean Breeze Hotel,?situated in a serene area in the heart of the Riviera Maya in Playa del Carmen,?is a boutique hotel surrounded by lush gardens and the backdrop of the Caribbean Sea.
Ocean Breeze Hotel offers an executive golf course, world class Spa Brio, an ocean view fitness center and more.
Sea Garden Hotel in Nuevo Vallarta offers pristine swimming pools, challenging golf courses and breathtaking ocean views.
Includes complimentary airport pick-up to either hotel.
Enjoy a 4-night stay for less than $50 per night.
Modern furnishings and bright, comfortable rooms make these hotels the perfect places for a family vacation.
Fine Print
Expires 12/19/2012.
Voucher cannot be redeemed until the day after deal closes.
Valid for up to 2 adults (must be 28 years of age or older) and 2 children (12 years of age and under).
Limit 1 certificate per household; may purchase 1 additional as gift. Not valid for group travel.
Valid for 5 days and 4 nights at either Ocean Breeze Riviera Maya Hotel at Playa del Carmen or the Sea Garden Hotel in Nuevo Vallarta.
Valid for a Standard Room.
Reservations subject to availability.?
This offer is provided by and scheduled through Mexico Travel Company. Bookings must be made by calling 888-488-9468 (toll free), Mon-Fri from 9am-7pm and Saturdays 9am-1pm (CST).
Reservations must be made at least 45 days in advance or a $50 fee may apply.
Reservations cancelled within 15 days of expected arrival date will incur $50 per room fee. Failure to arrive on confirmed date will result in reservation cancelled in its entirety. Additional cancellations penalties may apply.
Airfare and other travel expenses not included. Not all-inclusive.
Incidental expenses such as gratuities, service charges and/or any other personal expenses are not included.
Must provide a major credit card at check-in to cover cost of incidentals.
Must redeem in one visit. No cash value/ cash or credit back.
Not valid for retail sale and must forfeit any payments in the event of a cancellation as listed above.
You may cancel purchase if accommodations or facilities not available.
Blackout Dates: 04/01 to 04/14/2012; 11/21 to 11/28/2012; 12/20/2012 to 01/03/2013.
Mexico Travel Company reserves the right to substitute hotels/resorts of similar or superior quality to accommodate guest.
See the fine print that applies to all deals.
About This Deal
Last minute gift shopping? Planning a getaway for the new year? Or need an excuse to get out of town for rest and relaxation? Today's deal has been designed with your vacation needs in mind. A four night, five day stay at your choice of one of two Mexican destinations would normally cost $687, but today you can pick up this package to paradise for only $199. Choose your getaway to the Sea Garden Hotel in Nuevo Vallarta or the Ocean Breeze Riviera Maya Hotel in Playa del Carmen and start packing!
Your resort stay can accommodate up to two adults (must be 28 years of age or older) and two children (ages 12 or younger), so you can surprise a special someone and even bring the little ones along. The deal is good for almost a year, so you'll have ample time to make your travel arrangements for 2012. Here are some highlights of each resort and destination:
Sea Garden Hotel in Nuevo Vallarta: Near Puerto Vallarta, Nuevo Vallarta is a tourist development close to lots of activities and attractions. Nayarit's rainforest, a beautiful beach front and Puerto Vallarta's downtown area all offer something different for your stay- whether you want to explore, relax, or live up the nightlife. Golf courses are close by if you want to play a round. And the Sea Garden's sister hotel boasts the Brio Spa for your pampering needs. Surrounding restaurants offer everything from Mexican to Italian to Japanese. The hotel room you'll enjoy on your trip includes modern d?cor and comfortable furnishings. Amenities include: air conditioning, cable TV, drinking water and more.
Ocean Breeze Riviera Maya Hotel in Playa del Carmen: This boutique hotel is situated in a serene area in the heart of the Riviera Maya in Playa del Carmen. It is surrounded by lush gardens and the backdrop of the Caribbean Sea. The resort complex at Ocean Breeze Riviera Maya offers an executive golf course, spa and other attractions. Room amenities include satellite TV, high speed internet access, air conditioning, and more. Restaurants and bars on the property offer an assortment of dining options, or you can opt for room service and enjoy your meals in the comfort of your own room. And, of course, the area offers white sand beaches that are beautiful and inviting.
It's easy to see that both destinations offer a variety of activities and attractions, whether you're on a romantic getaway or treating your family to some much-needed fun. Plus, each resort offers complimentary airport pick up. See what these fans have to say about each hotel and their fond memories:
"The Ocean Breeze Hotel was everything we could have wanted in hotel! Great service, good location, clean rooms and great food. It's 10 minutes from Puerto Morelos and Playa del Carmen and 30 minutes from Cancun." - "Jane49785," TripAdvisor
"We love our stay at Ocean Breeze! We spent 10-days the beginning of April. Excellent room service, food, and very nice people. We loved location, hotel is situated in the jungle and it was really relaxing. Kids loved golf cart rides to the big pool at the Mayan palace area and enjoyed kid's club. Overall, we would like to go back." - "A Traveler from Denver," Expedia
"We cannot say enough about our week stay at the Sea Garden in Nuevo Vallarta. It was wonderful. Very quiet, clean and understated. The pool was by far our favorite. The view was spectacular." - "MeAndMyMan," TripAdvisor
"The Sea Garden is a wonderful gem. Not too big, and not too small. It was quiet and very relaxing. The pool area is nicely landscaped, very clean, and is big enough to be interesting but not crowded. The beach here is very clean and well kept as well." - "A Traveler from San Diego," Expedia
Company Info
Ocean Breeze or Sea Garden Hotels
888-488-9468
Website >
Locations
Sea Garden, Nuevo Vallarta
Av Paseo de las Moras s/n Nuevo Vallarta 63735, MX 00000 888-488-9468 Get Directions
Ocean Breeze, Playa del Carmen
Km 48 Carretera Federal 200 Playa del Carmen 77710, MX 00000 888-488-9468 Get Directions
This blog features observations from Joplin East Middle School communication arts teacher Randy Turner, formerly an award-winning reporter/editor for various Missouri newspapers. The comments on the blog do not represent the views of the Joplin R-8 School District. Send news items or comments to rturner229@hotmail.com
Still thinking the Cubs are going to get in on Prince Fielder? Think again.?David Kaplan of CSNChicago.com reports that Theo Epstein and Jed Hoyer are looking to completely blow things up and that Fielder is not in the offing:
?After speaking with several baseball sources over the past few days I am hearing that a complete and total rebuild of the Cubs is more likely than ever to take place during the remainder of the off-season ? [Sean]?Marshall along with several other players on the Cubs roster are all being shopped as?Theo Epstein,?Jed Hoyer, and company look to maximize their value as they look to completely overhaul the team.?
A weak farm system and no real parts that, right now, could form the core of a World Series winning team are what?s forcing their hand, Kaplan writes.
This obviously has big implications for the Cubs over the next couple of years. But boy howdy does it always have some implications for Prince Fielder?s market this winter. I mean really, where does he go?
A 1-year-old girl whose family was profiled on CNN.com died Tuesday after a seven-month struggle with a childhood cancer.
The stories of the child, Saoirse Craig Fitzgerald, and her mother, Kezia Fitzgerald, were?told this fall because they were both diagnosed with cancer - albeit different types - within five months of each other.
In the Fitzgerald family, a household of three, cancer struck twice.
Shortly after Kezia learned she had Hodgkin's lymphoma, her daughter was diagnosed in May with neuroblastoma, a childhood cancer that destroys a young nervous system by turning nerve cells into tumors. Cancer is "staged" to indicate its spread and Saoirse had stage 4, the furthest the disease can progress. ?Kezia had stage 3 cancer, which is now in remission.
Saoirse, who is shown in this photo gallery from the September story, was a curious, playful girl who loved petting the family dog, Fallon, cuddling with her parents and watching "Sesame Street."
The cancer she had, neuroblastoma, develops from tissues that control vital body functions like heart rate, blood pressure, digestion and hormones, according to U.S. National Library of Medicine. It's unclear what causes neuroblastoma, but researchers believe the genetic mutation that contributes to the cause occurs during pregnancy or soon after birth.
"This robbed me of my daughter,"??her father, Mike Fitzgerald said. ?"It'll never take away anything she stood for."
Despite? aggressive treatments, the neuroblastoma returned seemingly stronger each time.
Saoirse endured eight rounds of chemotherapy - many of them lasting for days. She endured the harsh chemicals and surgery that removed both her adrenal glands. ?She did what 1-year-olds do - smile, dole out high-fives to the hospital staff and chase after her mommy and daddy.
In November, the family received more bad news. Saoirse's cancer had returned after surgery, this time in her skull. Not a week later, her liver became enlarged and swollen, because the cancer had overtaken the organ.
Saoirse's breathing became labored. ?She couldn't sleep because she had to stay awake ?to breathe.
"It was labored and violent in the last few hours," her father said. "She was breathing 60-90 breaths a minute. All her energy was spent on breathing."
Her parents put on "Curious George" and "Sesame Street" to calm her. Looking at the images on her iPad, she uttered, "Elmo."
Doctors prepared for a risky intubation procedure, hoping that a breathing tube would help her.
Mike Fitzgerald crouched next to his daughter and whispered into her ear: "You're safe. It's OK to relax. It's OK to go to sleep. Doctors are going to look at you. Mommy and Daddy are right here."
Her eyes were swollen, but she made eye contact with her mommy and daddy.
At 6:47 a.m. Tuesday, Saoirse died.
Her memorial service will be held on Saturday. Guests are prohibited from wearing black.
Let's do the twist: Spiral proteins are efficient gene delivery agentsPublic release date: 15-Dec-2011 [ | E-mail | Share ]
Contact: Liz Ahlberg eahlberg@illinois.edu 217-244-1073 University of Illinois at Urbana-Champaign
CHAMPAIGN, Ill. Clinical gene therapy may be one step closer, thanks to a new twist on an old class of molecules.
A group of University of Illinois researchers, led by professors Jianjun Cheng and Fei Wang, have demonstrated that short spiral-shaped proteins can efficiently deliver DNA segments to cells. The team published its work in the journal Angewandte Chemie.
"The main idea is these are new materials that could potentially be used for clinical gene therapy," said Cheng, a professor of materials science and engineering, of chemistry and of bioengineering.
Researchers have been exploring two main pathways for gene delivery: modified viruses and nonviral agents such as synthetic polymers or lipids. The challenge has been to address both toxicity and efficiency. Polypeptides, or short protein chains, are attractive materials because they are biocompatible, fine-tunable and small.
"There are very good in vitrotransfection agents available, but we cannot use them in vivo because of their toxicity or because some of the complexes are too large," Cheng said. "Using our polypeptides, we can control the size down to the 200 nanometer range, which makes it a very interesting delivery system for in vivo applications."
A polypeptide called poly-L-lysine (PLL) was an early contender in gene delivery studies. PLL has positively charged side chains molecular structures that stem from each amino acid link in the polypeptide chain so it is soluble in the watery cellular environment.
However, PLL gradually fell into disuse because of its limited ability to deliver genes to the inside of cells, a process called transfection, and its high toxicity. Cheng postulated that PLL's low efficiency could be a function of its globular shape, as polypeptides with charged side chains tend to adopt a random coil structure, instead of a more orderly spiral helix.
"We never studied the connections of conformation with transfection efficiency, because we were never able to synthetically make materials containing both cationic charge and a high percentage of helical structures," Cheng said. "This paper demonstrated for the first time that helicity has a huge impact on transfection efficiencies."
Earlier this year, Cheng's group developed a method of making helical polypeptides with positively charged side chains. To test whether a helical polypeptide could be an efficient gene delivery agent, the group assembled a library of 31 helical polypeptides that are stable over a broad pH range and can bond to DNA for delivery. Most of them outperformed PLL and a few outstripped a leading commercial agent called polyethyleneimine (PEI), notorious for its toxicity although it is highly efficient. The helical molecules even worked on some of the hardest cells to transfect: stem cells and fibroblast cells.
"People kind of gave up on polypeptide-based materials for gene deliveries because PLL had low efficiency and high toxicity," Cheng said. "The polypeptide that we designed, synthesized and used in this study has very high efficiency and also well-controlled toxicities. With a modified helical polypeptide, we demonstrated that we can outperform many commercial agents."
The polypeptides Cheng and his co-workers developed can adopt helical shapes because the side chains are longer, so that the positive charges do not interfere with the protein's winding. The positive charges readily bind to negatively charged DNA, forming complexes that are internalized into cellular compartments called endosomes. The helical structures rupture the endosomal membranes, letting the DNA escape into the cell.
To confirm that the spiral polypeptide shape is the key to transfection, the researchers then synthesized two batches of the most efficient polypeptide: one batch with a helical shape, one with the usual random coil. The helical polypeptide far exceeded the random-coil polypeptide in both efficiency and stability.
"This demonstrates that the helicity is very important, because the polymer has exactly the same chemical makeup; the only difference is the structure," said Cheng, who also is associated with the Institute for Genomic Biology and the Beckman Institute for Advanced Science and Technology, both at the U. of I.
Next, the researchers plan to further explore their helical polypeptides' properties, especially their cell-penetrating abilities. They hope to control sequence and structure with precision for specific applications, including gene delivery, drug delivery, cell-membrane penetration and antimicrobial action.
###
The National Science Foundation and the National Institutes of Health supported this work. Fei Wang is a professor of cell and development biology and of bioengineering. Postdoctoral researchers Nathan Gabrielson, Lichen Yin and Dong Li and graduate student Hua Lu were co-authors of the paper.
Editor's note: To contact Jianjun Cheng, call 217-244-3924; email jianjunc@illinois.edu.
The paper, "Reactive and Bioactive Cationic ?-Helical Polypeptide Template for Nonviral Gene Delivery," is available online.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Let's do the twist: Spiral proteins are efficient gene delivery agentsPublic release date: 15-Dec-2011 [ | E-mail | Share ]
Contact: Liz Ahlberg eahlberg@illinois.edu 217-244-1073 University of Illinois at Urbana-Champaign
CHAMPAIGN, Ill. Clinical gene therapy may be one step closer, thanks to a new twist on an old class of molecules.
A group of University of Illinois researchers, led by professors Jianjun Cheng and Fei Wang, have demonstrated that short spiral-shaped proteins can efficiently deliver DNA segments to cells. The team published its work in the journal Angewandte Chemie.
"The main idea is these are new materials that could potentially be used for clinical gene therapy," said Cheng, a professor of materials science and engineering, of chemistry and of bioengineering.
Researchers have been exploring two main pathways for gene delivery: modified viruses and nonviral agents such as synthetic polymers or lipids. The challenge has been to address both toxicity and efficiency. Polypeptides, or short protein chains, are attractive materials because they are biocompatible, fine-tunable and small.
"There are very good in vitrotransfection agents available, but we cannot use them in vivo because of their toxicity or because some of the complexes are too large," Cheng said. "Using our polypeptides, we can control the size down to the 200 nanometer range, which makes it a very interesting delivery system for in vivo applications."
A polypeptide called poly-L-lysine (PLL) was an early contender in gene delivery studies. PLL has positively charged side chains molecular structures that stem from each amino acid link in the polypeptide chain so it is soluble in the watery cellular environment.
However, PLL gradually fell into disuse because of its limited ability to deliver genes to the inside of cells, a process called transfection, and its high toxicity. Cheng postulated that PLL's low efficiency could be a function of its globular shape, as polypeptides with charged side chains tend to adopt a random coil structure, instead of a more orderly spiral helix.
"We never studied the connections of conformation with transfection efficiency, because we were never able to synthetically make materials containing both cationic charge and a high percentage of helical structures," Cheng said. "This paper demonstrated for the first time that helicity has a huge impact on transfection efficiencies."
Earlier this year, Cheng's group developed a method of making helical polypeptides with positively charged side chains. To test whether a helical polypeptide could be an efficient gene delivery agent, the group assembled a library of 31 helical polypeptides that are stable over a broad pH range and can bond to DNA for delivery. Most of them outperformed PLL and a few outstripped a leading commercial agent called polyethyleneimine (PEI), notorious for its toxicity although it is highly efficient. The helical molecules even worked on some of the hardest cells to transfect: stem cells and fibroblast cells.
"People kind of gave up on polypeptide-based materials for gene deliveries because PLL had low efficiency and high toxicity," Cheng said. "The polypeptide that we designed, synthesized and used in this study has very high efficiency and also well-controlled toxicities. With a modified helical polypeptide, we demonstrated that we can outperform many commercial agents."
The polypeptides Cheng and his co-workers developed can adopt helical shapes because the side chains are longer, so that the positive charges do not interfere with the protein's winding. The positive charges readily bind to negatively charged DNA, forming complexes that are internalized into cellular compartments called endosomes. The helical structures rupture the endosomal membranes, letting the DNA escape into the cell.
To confirm that the spiral polypeptide shape is the key to transfection, the researchers then synthesized two batches of the most efficient polypeptide: one batch with a helical shape, one with the usual random coil. The helical polypeptide far exceeded the random-coil polypeptide in both efficiency and stability.
"This demonstrates that the helicity is very important, because the polymer has exactly the same chemical makeup; the only difference is the structure," said Cheng, who also is associated with the Institute for Genomic Biology and the Beckman Institute for Advanced Science and Technology, both at the U. of I.
Next, the researchers plan to further explore their helical polypeptides' properties, especially their cell-penetrating abilities. They hope to control sequence and structure with precision for specific applications, including gene delivery, drug delivery, cell-membrane penetration and antimicrobial action.
###
The National Science Foundation and the National Institutes of Health supported this work. Fei Wang is a professor of cell and development biology and of bioengineering. Postdoctoral researchers Nathan Gabrielson, Lichen Yin and Dong Li and graduate student Hua Lu were co-authors of the paper.
Editor's note: To contact Jianjun Cheng, call 217-244-3924; email jianjunc@illinois.edu.
The paper, "Reactive and Bioactive Cationic ?-Helical Polypeptide Template for Nonviral Gene Delivery," is available online.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
NEW YORK/SAN FRANCISCO (Reuters) ? Online games developer Zynga Inc scored badly as it went public on Friday, dashing hopes for the year's hottest tech IPO, as investors frowned on its over-reliance on Facebook, dimming growth prospects, and outsized control by CEO Mark Pincus.
Zynga's stock fell 5 percent below its $10 initial public offering price to close at $9.50 on Nasdaq on Friday, dealing losses to IPO buyers used to racking up gains on a stock's first day of trading.
Investors had eagerly awaited the IPO as a way to get a slice of Facebook's growth before the leading social networking website goes public, possibly in 2012. Zynga makes money on Facebook by selling virtual items such as jewelry and poker chips in its games such as "FarmVille" and "CityVille."
At least one analyst said on Friday that some investors may have been turned off by Chief Executive Mark Pincus' large voting stake and control over the company. He has a special class of shares that grants him 37 percent voting power even though his equity stake is much lower, and public shareholders will have less than 2 percent of votes.
"We believe that having a CEO/owner-controlled board is particularly dangerous for investors in young companies," said Cowen and Co analyst Doug Creutz.
Creutz, who has a neutral rating on the stock, added that history is full of examples of CEOs who have built young companies but cannot manage them when they mature.
Asked about his voting shares, Pincus told Reuters he decided to retain such huge control over Zynga because he believed from the start that he was the best person to lead the company.
"Investors who want to see the company deliver long-term value are going to be better served by the fact that I can continue to ensure the company keeps its focus on the long term and we don't let short-term swings and opportunities reduce that," he said in an interview.
Based on Friday's closing share price, the value of Pincus' holdings fell to $1.05 billion from $1.1 billion at the IPO price.
Friday's flop stunned investors who had expected a strong showing because the company is profitable, unlike other recent high profile Internet IPOs such as Groupon and Pandora.
"I was stunned when I saw this. This is a disaster for them. The way you're supposed to price deals is to give investors a 15 percent IPO discount to compensate them for the risk of backing a relatively new company," said Dan Niles, chief investment officer of AlphaOne Capital Partners, who did not buy shares.
"It makes me wonder about the underlying health of the market. IPOs like this can change the whole tenor of the market," he added.
Investors said Zynga's stock performance could hurt other private companies in the pipeline such as Yelp and even Facebook. Some investors regard Zynga's IPO as a proxy for Facebook, because 95 percent of its $828 million in revenue in the past nine months comes from Mark Zuckerberg's social network.
"Now we have an exciting IPO and people don't want it and that's a big concern for when Facebook comes out," said Jeff Sica, president and chief investment officer of SICA Wealth Management.
The cooling off in the IPO markets could hurt Facebook's estimated $100 billion valuation, BGC analyst Colin Gillis said.
Zynga's reliance on the platform was supposed to attract investors looking to bet on Facebook's growth. With Facebook's IPO expected to be at least several months away, Zynga is one of the few indirect ways to bet on the website's future.
Facebook takes a 30 percent cut of the revenue Zynga derives from the social network, which features more than 222 million monthly active Zynga users.
Zynga CEO Pincus said he was looking beyond the share price drop and said the company went public at the right time.
"We're going to focus on the products and business results we deliver in the next four to eight quarters and hope the stock market values and appreciates that as they see us deliver it," he said.
In San Francisco, hundreds of employees got to work early to watch Pincus ring the bell to open Nasdaq trading and wore T-shirts saying "I love play" featuring the ZNGA trading symbol printed on the sleeves. Cinnamon buns and hot cocoa were served before the ceremony.
CONCERNS WEIGH
The company, which competes with Electronic Arts, sold 100 million shares of Class A common stock at $10 per share in the IPO, roughly 11 percent of its shares on a diluted basis, at the top end of the $8.50 to $10 indicative range.
The IPO values Zynga at $8.9 billion. In November, the company had been valued at roughly $14 billion, according to an internal estimate in a regulatory filing.
But that lowered valuation may still have been too rich for some, said Sterne Agee analyst Arvind Bhatia.
Zynga's near $9 billion valuation is less than videogame maker Activision Blizzard Inc's $13.6 billion and higher than Electronic Arts Inc's $6.7 billion. In the last four quarters, Activision and Electronic Arts generated more revenue than Zynga.
Analysts and investors have also expressed concern over how it profits from less than 3 percent of its players who buy items in its free games.
Plus, its reliance on Facebook appears unhealthy to investors who want to see Zynga diversify its revenue sources. Pincus on Friday said the company's 13 million daily users of its mobile games is a good start, and doesn't trail its daily users on Facebook as much as people assume. Zynga had 50.5 million daily users on Facebook on Friday, according to AppData, a website which tracks Facebook applications.
Yet Zynga's growth rate of bookings - the money it makes up front when users buy items, is slowing - which most analysts said is a red flag and could hurt Zynga's future revenue.
Zynga is the second online games company selling virtual items to slip in its trading debut this week. On Wednesday, Nexon Co shares fell following its $1.2 billion IPO, which was Japan's biggest offering this year.
At $1 billion in proceeds, Zynga's IPO is still the largest from a U.S. Internet company since Google Inc raised $1.9 billion in 2004.
(Reporting By Liana B. Baker in New York and Alistair Barr in San Francisco)
Alibaba is beefing up content on its mobile operating system after announcing a partnership with DeNA that will see the Japanese firm?s Mobage mobile gaming series pre-loaded to?Aliyun OS?devices.
Owners of the upcoming K-touch W800 smartphone will be the first to reap the benefit of the arrangement, as part of which the device will have a dedicated Mobage icon on its homescreen. Other Aliyun devices, which may include the strongly rumoured iPad competitor, will follow suit with in-built Mobage support from early 2012.
Aliyun is a Linux-based operating system that is fully compatible with Android apps, and other web apps, but it is not based on the Google operating system, unlike Baidu?s rumoured Qiuishi OS. The operating system was thought to be launching before 2012, but no new information has been presented since its existence came to light earlier this year.
Alibaba has also revealed that it will work to provide access to DeNA?s?cross-device mobile game development engine for Mobage, through its own AliCloud?s cloud services. The companies believe that the use of the cloud will enable developers to work more efficiently in China, as Isao Moriyasu, president and representative director of DeNA, explains.
We believe our alliance with AliCloud will bring tremendous opportunities to both companies. Through AliCloud?s innovative mobile OS and cloud services, DeNA will be able to deliver Mobage to even larger user base in China, while also allowing promising Chinese developers to expand their reach to our global user base.
Localisation is a key step to making mobile content, and any other content, for that matter, relevant in China as we?ve seen with Rovio?s Angry Birds franchise ? which recently launched a China office ? and Halfbrick?s Fruit Slice, the Chinese version of which generated a cool $6 million in just 3 months.
Mobage has been available in China since July, when, as Penn Olson reported, DeNA rolled its flagship mobile gaming platform into overseas markets for the first time. As well as China, English-speaking areas of the world were added, as the company looked to translate its success in Japan to the worldwide market.
The company has also taken its first step into Europe through a business development link-up in Germany, while it gained global attention when it purchased US iPhone development specialist Ngmoco for $400 million last year, as Venture Beat reported?at the time.
Mobile gaming is?already massive?in Japan and, with DeNA and its rival GREE both pushing their reach globally, the industry looks set for increased growth on an international scale.