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.
The newly redesigned Galaxy Tab 10.1N is different enough says German Judge - bit.ly/uHMT99 
AndroidSPIN 
![[ Back to EurekAlert! ]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_v5o4cIaHoCVZc1Y0Ct580LtPWMYMg1rRkLVgjAslSnb5y_P-mS1fzGDsujuaWr2Ydaydu14FcTV8jP5abkFfz2Ud-CFvVyw3xwrXYEq38=s0-d){kind=small}
Public release date: 15-Dec-2011
Share ]