Salesforce.com is to create more than 100 New Jobs in Dublin

Are you in your dream job? Salesforce.com is hiring!

Growing demand for the social enterprise drives salesforce.com?s expansion in Dublin

DUBLIN Ireland ? 28th June, 2012 ? Salesforce.com, the enterprise cloud computing company (http://www.salesforce.com/cloudcomputing/), today announced plans to add more than 100 new jobs in Dublin to meet the demands of continued growth in Ireland. The company is immediately looking to hire qualified professionals in sales, marketing, IT and customer support functions.

The announcement was made this morning in Dublin by Ireland's Minister for Jobs, Enterprise and Innovation, Richard Bruton T.D and salesforce.com?s EMEA chairman, Dr. Steve Garnett.
IDA Ireland has worked with salesforce.com on its developments in Ireland since it first established operations in Dublin in 2000.

Recently named 27th on Fortune?s 100 best places to work list and recognised by Forbes as the most world?s most innovative company, salesforce.com is one of the global technology industry?s fastest growing companies and is seen as a pioneer and visionary leader.

Comments on the news:

• "The Government is targeting high-growth companies and high-growth sectors as part of our Action Plan for Jobs. Today's very welcome announcement that salesforce.com, a dynamic company operating at the cutting edge of social, mobile and cloud computing, is creating 100 additional jobs in Dublin shows what is possible in these sectors.

I am determined to ensure that we continue to take advantage of our ICT strengths to attract more investments and create the jobs we need,? said Richard Bruton, T.D., Minister for Jobs, Enterprise and Innovation.

• "Salesforce.com is driving a massive transformation in the technology industry, showing companies the power of social and mobile cloud computing. Ireland has played a key role in our success and we are delighted to be able to expand our reach in the region through the creation of an additional 100 jobs. We are actively looking for talented individuals to join us as we help more companies transform into social enterprises,? said Dr. Steve Garnett, Chairman EMEA, salesforce.com.
  ?
• ?Salesforce.com is very much a pioneer of cloud computing and its growth over recent years has been very impressive. Ireland has been a key location for the company in its global expansion and it is great to see this further enhanced in this latest expansion,?? said Barry O?Leary, Chief Executive Officer, IDA Ireland.

Find your dream job
Salesforce.com is holding an exclusive #dreamjob recruitment event in Dublin on the evening of the 5th July 2012 at The Morrison Hotel. To find out more about working at salesforce.com, people can register - in confidence ? at www.salesforce.com/eu/openday or check out the available positions on www.salesforce.com/eu/careers.?

The Social Enterprise Revolution
Trends in cloud computing are being driven by the social revolution that is taking place today. The number of social networking users has surpassed e-mail users. Nearly a quarter of all time spent online is spent on social networks like Facebook. People access the Internet more from mobile devices than from desktops. Salesforce.com is helping companies meet the challenge of this social revolution with its social enterprise solution. Today, companies must change the way they collaborate, communicate and share information with customers and employees to stay competitive. By leveraging salesforce.com?s social and mobile cloud technologies to develop social customer profiles and create employee and customer social networks, companies can transform themselves into social enterprises.

The demand for the social enterprise has fuelled significant growth in salesforce.com?s customer base and the company now has more than 20,000 customers in Europe. Salesforce.com has been investing in Ireland since 2000 and the Dublin office is the European hub for salesforce.com?s commercial sales operation.

Follow @Salesforce on Twitter and Suggested Tweets:
If you?d like to tweet about the salesforce.com recruitment open day in Dublin, here are some suggested tweets to send to your followers:
??Click to Tweet:? Salesforce.com recruitment open day in Dublin on July 5th ? Find your #dreamjob http://bit.ly/LVIQfF via @salesforce
??Click to Tweet: Salesforce.com is hiring! Visit their recruitment open day in Dublin on July 5th? http://bit.ly/LVIQfF via @salesforce

Additional Resources
??Interested in working at one of the best places to work? Check out our recruiting page for Ireland: http://www.salesforce.com/eu/campaigns/openday/
??Follow @salesforce on Twitter.
??Like salesforce.com on Facebook: http://www.facebook.com/Salesforce.
??A community of good people doing great things: The Salesforce.com Foundation: http://www.salesforcefoundation.org.

About Salesforce.com
With more than 100,000 customers, salesforce.com is the enterprise cloud computing company that is leading the shift to the social enterprise. Social enterprises leverage social, mobile and open cloud technologies to put customers at the heart of their business. Based on salesforce.com's real-time, multitenant architecture, the company's platform and application services allow customers to:

• Create employee social networks with Salesforce Chatter, Salesforce Rypple and Salesforce Force.com.
• Develop customer social networks with the Salesforce Sales Cloud, Salesforce Data.com, Salesforce Service Cloud, and Salesforce Site.com.
• Connect with customers on public social networks with Salesforce Heroku and Salesforce Radian6.
• Empower small businesses to become social enterprises with Salesforce Desk.com and Salesforce Do.com.
• Extend a company's social enterprise with apps from the leading enterprise app marketplace, AppExchange.
• Run apps on Database.com, the first social enterprise database.

Any unreleased services or features referenced in this or other press releases or public statements are not currently available and may not be delivered on time or at all. Customers who purchase salesforce.com applications should make their purchase decisions based upon features that are currently available. Salesforce.com has headquarters in San Francisco, with offices in Europe and Asia, and trades on the New York Stock Exchange under the ticker symbol ?CRM.? For more information please visit http://salesforce.com, or call 1-800-NO-SOFTWARE.

?2012 salesforce.com, inc.? All rights reserved. Salesforce.com, Salesforce, Chatter, Sales Cloud, Service Cloud, Radian6, Jigsaw, AppExchange, Force.com, Heroku, and all associated logos are trademarks of salesforce.com, inc. in the United States and other countries. Salesforce.com offers its Siteforce products and services in Germany under the Force.com Sites trademark. Other names used herein may be trademarks of their respective owners.? Other names used herein may be trademarks of their respective owners.

Media Contacts for this Announcement:
Salesforce.com
Fiona Williams
+44 (0)7717 732067
fwilliams@salesforce.com

Department of Jobs, Enterprise and Innovation
Press Office:? +353 1 631 2200 or press.office@djei.ie

IDA Ireland
Press office +353 1 603 4226

MKC Communications
Tim Kinsella / Julie Dilger
+353 1 703 8600
tim@mkc.ie / julie@mkc.ie
?

Source: http://feedproxy.google.com/~r/idapress/~3/BcxDF67fD_8/index.xml

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Lawyer: US hunger striker in Dubai eating again

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Source: http://news.yahoo.com/lawyer-us-hunger-striker-dubai-eating-again-161532074.html

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Scalia critics say justice too political last term

FILE - In this March 8, 2012 file phoo, Supreme Court Justice Antonin Scalia speaks at Wesleyan University in Middletown, Conn. Scalia drew unusually critical attention during this past Supreme Court term for comments he made in court and in his writing that seemed to some more political than judicial. (AP Photo/Jessica Hill, File)

FILE - In this March 8, 2012 file phoo, Supreme Court Justice Antonin Scalia speaks at Wesleyan University in Middletown, Conn. Scalia drew unusually critical attention during this past Supreme Court term for comments he made in court and in his writing that seemed to some more political than judicial. (AP Photo/Jessica Hill, File)

WASHINGTON (AP) ? Justice Antonin Scalia drew unusually critical attention during this past Supreme Court term for comments he made in court and in his writing that seemed to some more political than judicial.

His dissent in the Arizona immigration case contained a harsh assessment of the Obama administration's immigration policy and prompted a public rebuke from a fellow Republican-appointed judge.

Scalia's aggressive demeanor during argument sessions even earned him some gentle teasing from his closest personal friend on the court. Justice Ruth Bader Ginsburg, speaking at a Washington convention, said the term's high-profile cases may explain why Scalia "called counsel's argument 'extraordinary' no fewer than 10 times."

The 76-year-old Scalia is a gifted writer with a razor wit and willingness to do battle with those on the other side of an issue. Those qualities have made him a powerful voice, an entertaining presence and a magnet for criticism on the court for more than 25 years. Even with that vivid background, some of Scalia's recent remarks stood out in the eyes of court observers.

Ten lawyers who appear regularly before the Supreme Court, including two former Scalia law clerks, were interviewed for this story and said they too had taken note of Scalia's recent comments. But mindful that they might appear before the high court or be in a position to submit legal briefs, they all declined to be identified by name.

Measured by wins and losses, the court term did not end well for Scalia. He was on the losing end of the court's biggest cases involving health care, immigration, lying about military medals and prison sentences, both for crack cocaine offenders and juvenile killers.

The last words Scalia uttered in court this term dealt with his disagreement with the court's majority in a decision that watered down Arizona's crackdown on illegal immigrants.

Summarizing his views in court, Scalia commented on President Barack Obama's recent announcement changing the deportation rules for some children of illegal immigrants. And in his written opinion, he referenced anti-free-black laws of slave states as a precedent for state action on immigration. Both drew critical notice.

"The president said at a news conference that the new program is 'the right thing to do' in light of Congress' failure to pass the administration's proposed revision of the Immigration Act. Perhaps it is, though Arizona may not think so. But to say, as the court does, that Arizona contradicts federal law by enforcing applications of the Immigration Act that the president declines to enforce boggles the mind," Scalia said.

The outcry over his reference to Obama's announcement was immediate and included a call by liberal Washington Post columnist E.J. Dionne for Scalia to resign. Conservative Judge Richard Posner of the 7th U.S. Circuit Court of Appeals in Chicago, who was appointed by President Ronald Reagan, contributed this passage to Slate magazine's annual end-of-term discussion:

"These are fighting words. The nation is in the midst of a hard-fought presidential election campaign; the outcome is in doubt. Illegal immigration is a campaign issue. It wouldn't surprise me if Justice Scalia's opinion were quoted in campaign ads. The program that appalls Justice Scalia was announced almost two months after the oral argument in the Arizona case. It seems rather a belated development to figure in an opinion in the case," wrote Posner, who had taken Scalia to task in the past.

Doug Kmiec, a conservative legal scholar who backed Obama's election in 2008 and served as his ambassador to Malta, said, "To broadly assert, as Justice Scalia seems to do in his Arizona dissent, that the Obama administration's enforcement priorities are 'too lax,' substitutes the unelected Antonin Scalia for the elected Barack Obama."

Scalia's defenders say the criticism is misplaced. They say the justice was doing something much more familiar and common, attacking the majority opinion by Justice Anthony Kennedy. "He really wasn't criticizing the Obama administration's position. He was just using it as a timely example of why he thought his position was the better one in the Arizona case," said Brian Fitzpatrick, a Vanderbilt University law professor who once served as a law clerk to Scalia.

Separately, in defending the tough Arizona law, Scalia's written dissent refers to the laws of Southern slave states that excluded freed blacks to support the notion that states had control over immigration in the era before Congress enacted national legislation. Liberal commentators seized on that reference as a particularly bizarre twist in an otherwise angry opinion.

But Scalia's supporters say the justice is held to a different standard in the media than other justices. Ginsburg, for instance, won wide praise when she used her dissent in a sex discrimination case in 2007 to urge Congress to take action to undo the court's decision.

During the three days of health care arguments in March, Scalia spoke more than anyone else, mainly posing hostile questions to defenders of the law, according to a study of the arguments.

In an exchange with Solicitor General Donald Verrilli Jr., he left little doubt about what he thought of the eventual winning argument that the individual insurance requirement could be found constitutional under Congress' taxing powers.

"You're saying that all the discussion we had earlier about how this is one big uniform scheme and the Commerce Clause, blah, blah, blah, it really doesn't matter. This is a tax and the Federal Government could simply have said, without all of the rest of this legislation, could simply have said, everybody who doesn't buy health insurance at a certain age will be taxed so much money, right?" Scalia asked.

Eventually, Verrilli said, "It is justifiable under its tax power."

"Okay. Extraordinary," Scalia said.

The next day, he said the court should not have to go through each and every page of the massive law to sort out what stays and what goes should the justices invalidate the requirement that people carry insurance.

"What happened to the Eighth Amendment?" Scalia asked, referring to the Constitution's ban on cruel and unusual punishment. "You really expect us to go through 2,700 pages?"

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/386c25518f464186bf7a2ac026580ce7/Article_2012-07-04-Scalia/id-d17cef3b6368495b99be95bd08dcf81c

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GM talking with Facebook about advertising again: sources

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Source: http://news.yahoo.com/gm-talking-facebook-advertising-again-sources-204042219--sector.html

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CERN scientists discover new subatomic particle

GENEVA (Reuters) - Scientists at Europe's CERN research center have found a new subatomic particle, a basic building block of the universe, which appears to be the boson imagined and named half a century ago by theoretical physicist Peter Higgs.

"We have reached a milestone in our understanding of nature," CERN director general Rolf Heuer told a gathering of scientists and the world's media near Geneva on Wednesday.

"The discovery of a particle consistent with the Higgs boson opens the way to more detailed studies, requiring larger statistics, which will pin down the new particle's properties, and is likely to shed light on other mysteries of our universe."

Two independent studies of data produced by smashing proton particles together at CERN's Large Hadron Collider produced a convergent near-certainty on the existence of the new particle.

It is unclear that it is exactly the boson Higgs foresaw, which by bestowing mass on other matter helps explain the way the universe was ordered after the chaos of Big Bang.

But addressing scientists assembled in the CERN auditorium, Heuer posed them a question: "As a layman, I would say I think we have it. Would you agree?" A roar of applause said they did.

For some, there was no doubt the Higgs boson is found: "It's the Higgs," said Jim Al-Khalili of Surrey University, a British physicist and popular broadcaster. "The announcement from CERN is even more definitive and clear-cut than most of us expected.

"Nobel prizes all round."

Higgs, now 83, from Edinburgh University was among six theorists who in the early 1960s proposed the existence of a mechanism by which matter in the universe gained mass. Higgs himself argued that if there were an invisible field responsible for the process, it must be made up of particles.

He and some of the others were at CERN to welcome news of what, to the embarrassment of many scientists, some commentators have labelled the "God particle", for its role in turning the Big Bang into an ordered universe. Clearly overwhelmed, his eyes welling up, Higgs told the symposium of fellow researchers: "It is an incredible thing that it has happened in my lifetime."

Scientists see confirmation of his theory as accelerating investigations into the still unexplained "dark matter" they believe pervades the universe and into the possibility of a fourth or more dimensions, or of parallel universes. It may help in resolving contradictions between their model of how the world works at the subatomic level and Einstein's theory of gravity.

END OF AN ERA

"It is very satisfying," Higgs told Reuters. "For me personally it's just the confirmation of something I did 48 years ago," he said of the achievement of the thousands who labored on the practical experimental work which had, finally, confirmed what he and others had described with mathematics.

"I had no expectation that I would still be alive when it happened," he said of the speed with which they found evidence.

"For physics, in one way, it is the end of an era in that it completes the Standard Model," he said of the basic theory physicists currently use to describe what they understand so far of a cosmos built from 12 fundamental particles and four forces.

CERN's Large Hadron Collider is the world's biggest and most powerful particle accelerator. Two beams of protons are fired in opposite directions around the 27-km (17-mile) looped pipe built under the Swiss-French border before smashing into each other.

The collisions, which mimic the moments just after the Big Bang, throw off debris signals picked up by a vast complex of detectors and the data is examined by banks of computers.

The two separate CERN teams worked independently through that data, hunting for tiny divergences which might betray the existence of the new boson, a class of particle that includes the photon, associated with light. The class is named in honor of Albert Einstein's Indian collaborator Satyendra Nath Bose.

Both teams found strong signals of the new particle at around 125 to 126 gigaelectron volts (GeV) - a unit of mass-energy. That makes it some 130-140 times heavier than a proton.

Scientists struggling to explain the theory have likened Higgs particles to a throng of paparazzi photographers; the greater the "celebrity" of a passing particle, the more the Higgs bosons get in its way and slow it down, imparting it mass; but a particle such as a photon of light is of no interest to the paparazzi and passes through easily - a photon has no mass.

Presenting the results, Joe Incandela at CERN showed off two peaks on a graph of debris hitting the detectors, which he said revealed the hitherto unseen presence of the enigmatic particle. "That is what we are sure is the Higgs," a CERN scientist said.

LESS THAN ONE IN A MILLION

"It's a boson!" headlined Britain's Science and Technology Facilities Council in a statement on the role its researchers had played in the delivery of the "dramatic 5 sigma signal" for the existence of the long-sought particle.

Five sigma, a measure of probability reflecting a less than one in a million chance of a fluke in the data, is a widely accepted standard for scientists to agree the particle exists.

"The fact that both our teams have independently come to the same results is very powerful," Oliver Buchmueller, a senior physicist on one of the research teams, told Reuters.

"We know it is a new boson. But we still have to prove definitively that it is the one that Higgs predicted."

"If I were a betting man, I would bet that it is the Higgs. But we can't say that definitely yet. It is very much a smoking duck that walks and quacks like the Higgs. But we now have to open it up and look inside before we can say that it is indeed the Higgs."

Al-Khalili said the researchers' caution was extreme: "Cutting through all the jargon about sigmas and decay channels, the bottom line is that CERN have indeed discovered the Higgs boson," he said. "In my view, if it looks like the Higgs, smells like the Higgs and is exactly what we expected from the Higgs, then it's the Higgs."

UNIVERSAL THEORY

The Higgs theory explains how particles clumped together to form stars, planets and life itself. Without the Higgs boson, the universe would have remained a formless soup of particles shooting around at the speed of light, the theory goes.

It is the last undiscovered piece of the Standard Model that describes the fundamental make-up of the universe. The model is for physicists what the theory of evolution is for biologists.

What scientists do not yet know from the latest findings is whether the particle they have discovered is the Higgs boson as exactly described by the Standard Model. It could be a variant of the Higgs idea or an entirely new subatomic particle that could force a rethink on the fundamental structure of matter.

The last two possibilities are, in scientific terms, even more exciting.

Packed audiences of particle physicists, journalists, students and even politicians filled conference rooms in Geneva, London and a major physics conference in Melbourne, Australia, to hear the announcement.

Despite the excitement, physicists cautioned that there was still much to learn: "We have closed one chapter and opened another," said Peter Knight of Britain's Institute of Physics.

Paul Nurse, president of Britain's science academy The Royal Society, said: "This is a big day for science and for human achievement ... Today moves us a step closer to a fuller understanding of the very stuff of which the universe is made."

Higgs himself called it a great achievement for CERN's collider. Without it, his ideas would remain just a paper theory and he conceded that he personally was never cut out for laboratory experimentation: "I certainly did some lab work as a schoolboy in Bristol," he told Reuters. "I was incompetent."

(Additional reporting by Rosalba O'Brien in London and Sonali Paul in Melbourne; Writing by Alastair Macdonald)

Source: http://news.yahoo.com/scientists-unveil-milestone-higgs-boson-hunt-044513533.html

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New brain receptor for drug 'fantasy' identified

ScienceDaily (July 2, 2012) ? Researchers are closer to understanding the biology behind GHB, a transmitter substance in the brain, best known in its synthetic form as the illegal drug fantasy.

In the 1960s, gamma-hydroxybutyric acid (GHB) was first discovered as a naturally occurring substance in the brain. Since then it has been manufactured as a drug with a clinical application and has also developed a reputation as the illegal drug fantasy and as a date rape drug. Its physiological function is still unknown.

Now a team of researchers at the Department of Drug Design and Pharmacology at the University of Copenhagen has shown for the first time exactly where the transmitter substance binds in the brain under physiologically relevant conditions. The results have recently been published in the Proceedings of the National Academy of Sciences.

"We have discovered that GHB binds to a special protein in the brain -- more specifically a GABA_A-receptor. The binding is strong even at very low dosage. This suggests that we have found the natural receptor, which opens new and exciting research opportunities, in that we have identified an important unknown that can provide the basis for a full explanation of the biological significance of the transmitter," says Laura Friis Eghorn, PhD student.

Illegal use and possible antidote

Fantasy is also used as a so-called date rape drug, because in moderate amounts it has sedative, sexually stimulating and soporific effects. The compound is also abused for its euphoric effect, but in combination with alcohol, for example, it is a deadly cocktail that can lead to a state of deep unconsciousness or coma.

"GHB is registered for use as a drug to treat alcoholism and certain types of sleep disorders, but the risk of abuse presents difficulties. In the long-term, understanding how GHB works will enable us to develop new and better pharmaceuticals with a targeted effect in the brain, without the dangerous side-effects of fantasy," explains Laura Friis Eghorn, Department of Drug Design and Pharmacology.

Fantasy is an extremely toxic euphoriant, because the difference between a normal intoxicating dose and a fatal dose is so small. A better understanding of the biological mechanisms behind GHB-binding in the brain will benefit research into a life-saving antidote for this drug. Today there is no known antidote.

Statistics from Denmark in 2010 show that 8-10 percent of young people who frequent night clubs have had experience with Fantasy. However, since the drug is often also used in private for its sedative effect, it is difficult to estimate the extent of abuse.

Researchers on a targeted fishing expedition

The new research findings are the result of a collaboration between researchers at the University of Sydney in Australia and medicinal chemists at the Faculty of Health and Medical Sciences:

"Our chemist colleagues designed and produced special ligands -- that are mimics of GHB in several variations. This enabled us to go on a targeted fishing expedition in the brain. We have slowly found our way to the receptor, which we have also been able to test pharmacologically. In itself, it is not unusual to find new receptors in the brain for known compounds. However, when we find a natural match rooted in the brain's transmitter system, the biological implications are extremely interesting," explains Petrine Wellendorph, associate professor and head of the responsible research group that produced the pioneering results.

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Story Source:

The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Nathan Absalom, Laura F. Eghorn, Inge S. Villumsen, Nasiara Karim, Tina Bay, Jesper V. Olsen, Gitte M. Knudsen, Hans Br?uner-Osborne, Bente Fr?lund, Rasmus P. Clausen, Mary Chebib, and Petrine Wellendorph. ?4?? GABAA receptors are high-affinity targets for ?-hydroxybutyric acid (GHB). Proceedings of the National Academy of Sciences., July 2, 2012 DOI: 10.1073/pnas.1204376109

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/wI5MI_On4LA/120702192510.htm

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Researchers improve living tissues with 3-D printed vascular networks made from sugar

Researchers improve living tissues with 3-D printed vascular networks made from sugar

Monday, July 2, 2012

Researchers are hopeful that new advances in tissue engineering and regenerative medicine could one day make a replacement liver from a patient's own cells, or animal muscle tissue that could be cut into steaks without ever being inside a cow. Bioengineers can already make 2D structures out of many kinds of tissue, but one of the major roadblocks to making the jump to 3D is keeping the cells within large structures from suffocating; organs have complicated 3D blood vessel networks that are still impossible to recreate in the laboratory.

Now, University of Pennsylvania researchers have developed an innovative solution to this perfusion problem: they've shown that 3D printed templates of filament networks can be used to rapidly create vasculature and improve the function of engineered living tissues.

The research was conducted by a team led by postdoctoral fellow Jordan S. Miller and Christopher S. Chen, the Skirkanich Professor of Innovation in the Department of Bioengineering at Penn, along with Sangeeta N. Bhatia, Wilson Professor at the Massachusetts Institute of Technology, and postdoctoral fellow Kelly R. Stevens in Bhatia's laboratory.

Their work was published in the journal Nature Materials.

Without a vascular system ? a highway for delivering nutrients and removing waste products ? living cells on the inside of a 3D tissue structure quickly die. Thin tissues grown from a few layers of cells don't have this problem, as all of the cells have direct access to nutrients and oxygen. Bioengineers have therefore explored 3D printing as a way to prototype tissues containing large volumes of living cells.

The most commonly explored techniques are layer-by-layer fabrication, or bioprinting, where single layers or droplets of cells and gel are created and then assembled together one drop at a time, somewhat like building a stack of LEGOs.

Such "additive manufacturing" methods can make complex shapes out of a variety of materials, but vasculature remains a major challenge when printing with cells. Hollow channels made in this way have structural seams running between the layers, and the pressure of fluid pumping through them can push the seams apart. More important, many potentially useful cell types, like liver cells, cannot readily survive the rigors of direct 3D bioprinting.

To get around this problem, Penn researchers turned the printing process inside out.

Rather than trying to print a large volume of tissue and leave hollow channels for vasculature in a layer-by-layer approach, Chen and colleagues focused on the vasculature first and designed free-standing 3D filament networks in the shape of a vascular system that sat inside a mold. As in lost-wax casting, a technique that has been used to make sculptures for thousands of years, the team's approach allowed for the mold and vascular template to be removed once the cells were added and formed a solid tissue enveloping the filaments.

"Sometimes the simplest solutions come from going back to basics," Miller said. "I got the first hint at this solution when I visited a Body Worlds exhibit, where you can see plastic casts of free-standing, whole organ vasculature."

This rapid casting technique hinged on the researchers developing a material that is rigid enough to exist as a 3D network of cylindrical filaments but which can also easily dissolve in water without toxic effects on cells. They also needed to make the material compatible with a 3D printer so they could make reproducible vascular networks orders of magnitude faster, and at larger scale and higher complexity, than possible in a layer-by-layer bioprinting approach.

After much testing, the team found the perfect mix of material properties in a humble material: sugar. Sugars are mechanically strong and make up the majority of organic biomass on the planet in the form of cellulose, but their building blocks are also typically added and dissolved into nutrient media that help cells grow.

"We tested many different sugar formulations until we were able to optimize all of these characteristics together," Miller said. "Since there's no single type of gel that's going to be optimal for every kind of engineered tissue, we also wanted to develop a sugar formula that would be broadly compatible with any cell type or water-based gel."

The formula they settled on ? a combination of sucrose and glucose along with dextran for structural reinforcement ? is printed with a RepRap, an open-source 3D printer with a custom-designed extruder and controlling software. An important step in stabilizing the sugar after printing, templates are coated in a thin layer of a degradable polymer derived from corn. This coating allows the sugar template to be dissolved and to flow out of the gel through the channels they create without inhibiting the solidification of the gel or damaging the growing cells nearby. Once the sugar is removed, the researchers start flowing fluid through the vascular architecture and cells begin to receive nutrients and oxygen similar to the exchange that naturally happens in the body.

The whole process is quick and inexpensive, allowing the researchers to switch with ease between computer simulations and physical models of multiple vascular configurations.

"This new platform technology, from the cell's perspective, makes tissue formation a gentle and quick journey," Chen said, "because cells are only exposed to a few minutes of manual pipetting and a single step of being poured into the molds before getting nourished by our vascular network."

The researchers showed that human blood vessel cells injected throughout the vascular networks spontaneously generated new capillary sprouts to increase the network's reach, much in the way blood vessels in the body naturally grow. The team then created gels containing primary liver cells to test whether their technique could improve their function.

When the researchers pumped nutrient-rich media through the gel's template-fashioned vascular system, the entrapped liver cells boosted their production of albumin and urea, natural components of blood and urine, respectively, which are important measures of liver-cell function and health. There was also clear evidence of increased cell survival around the perfused vascular channels.

And theoretical modeling of nutrient transport in these perfused gels showed a striking resemblance to observed cell-survival patterns, opening up the possibility of using live-cell data to refine computer models to better design vascular architectures.

Though these engineered tissues were not equivalent to a fully functioning liver, the researchers used cell densities that approached clinical relevance, suggesting that their printed vascular system could eventually be used to further research in lab-grown organs and organoids.

"The therapeutic window for human-liver therapy is estimated at one to 10 billion functional liver cells," Bhatia said. "With this work, we've brought engineered liver tissues orders of magnitude closer to that goal, but at tens of millions of liver cells per gel we've still got a ways to go.

"More work will be needed to learn how to directly connect these types of vascular networks to natural blood vessels while at the same time investigating fundamental interactions between the liver cells and the patterned vasculature. It's an exciting future ahead."

With promising indications that their vascular networks will be compatible with all types of cells and gels, the team believes their 3D printing method will be a scalable solution for a wide variety of cell- and tissue-based applications because all organ vasculature follows similar architectural patterns.

"Cell biologists like the idea of 3D printing to make vascularized tissues in principle, but they would need to have an expert in house and highly specialized equipment to even attempt it," Miller said. "That's no longer the case; we've made these sugar-based vascular templates stable enough to ship to labs around the world."

Beyond integrating well with the world of tissue engineering, the researchers' work epitomizes the philosophy that drives much of the open source 3D printing community.

"We launched this project from innovations rooted in RepRap and MakerBot technology and their supporting worldwide communities," Miller said. "A RepRap 3D printer is a tiny fraction of the cost of commercial 3D printers, and, more important, its open-source nature means you can freely modify it. Many of our additions to the project are already in the wild."

Several of the custom parts of the RepRap printer the researchers used to make the vascular templates were printed in plastic on another RepRap. Miller will teach a class on building and using these types of printers at a workshop this summer and will continue tinkering with his own designs.

"We want to redesign the printer from scratch and focus it entirely on cell biology, tissue engineering and regenerative medicine applications," Miller said.

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University of Pennsylvania: http://www.upenn.edu/pennnews

Thanks to University of Pennsylvania for this article.

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Source: http://www.labspaces.net/121396/Researchers_improve_living_tissues_with___D_printed_vascular_networks_made_from_sugar

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