VA, Brown dedicate neurorestoration center

Officials and some famous patients gathered Friday morning, Oct. 26, 2012, to dedicate the new $4.5-million Center for Neurorestoration and Neurotechnology at the Providence Veterans Administration Medical Center. The CfNN’s scientific leadership is jointly appointed by the VA and Brown.

PROVIDENCE, R.I. [Brown University] — The Providence Veterans Administration Medical Center today announced a new research center, entirely led by scientists jointly affiliated with Brown University, that will develop and test technologies and therapies to help veterans with brain disorders, psychiatric conditions, and limb loss.

The VA funded the new Center of Excellence for Neurorestoration and Neurotechnology, with $4.5 million over five years. The CfNN involves more than 30 researchers overall, including some based at Butler Hospital and affiliated with Rhode Island Hospital and Massachusetts General Hospital.

“The VA Center for Neurorestoration and Neurotechnology brings together an exceptional group of scientists, clinicians, and engineers who carry out advanced research that’s leading to the latest cutting-edge technology and the newest therapies,” said John Donoghue, professor of neuroscience and engineering Brown and a research scientist at the VA, who directs the CfNN and the Brown Institute for Brain Science. “The research aims to restore the ability of our veterans to pursue fulfilling and independent lives.”

The CfNN is organized around two cores to support clinical trials and brain imaging, including Brown’s magnetic resonance imaging lab. It focuses on four areas of research: The BrainGate brain-computer interface to help people with severe paralysis; advancing prosthetics for upper-limb amputees; robotic- and computer-assisted rehabilitation for patients with strokes, multiple sclerosis, and other disorders; and neuromodulation technologies, such as electrical and magnetic brain stimulation to treat chronic pain, depression, post-traumatic stress disorder, and other psychiatric disorders.

In a statement, Brown President Christina Paxson praised that mission.

“Advancing science to restore health and quality of life for people with neurological disorders and limb loss is a tremendously inspiring research mission,” Paxson said. “Brown University is proud join with our longtime partners at the Providence VA Medical Center in dedicating this new center. This public investment in a meaningful collaboration between government, academic, and hospital-based researchers has the potential to yield many beneficial innovations for veterans and others.”

In his remarks Donoghue noted that all four research projects are already engaged in clinical trials where innovations are being tested and translated with real patients.

Credit: David Orenstein/Brown University

A Historic Meeting

But for all the speeches on the program, which also included remarks by Gov. Lincoln Chafee, Dr. Joel Kupersmith, chief research officer for the U.S. Department of Veterans Affairs, and Dr. Glenn Tung, associate dean of the Alpert Medical School, the loudest applause came at the very end when the two participants in the BrainGate research reported in the Nature paper in May were able to meet for the first time. Patients Bob (known in the paper as “T2”) came in from Connecticut and Cathy (known as “S3”) from Massachusetts.

Providence VA Chaplain Daniel Cottrell foreshadowed the meaning of the moment in his invocation: “May the mysteries unlocked not only be the success of science but the triumph of the human spirit.”

By David Orenstein

How silver turns people blue

Ingesting silver — in antimicrobial health tonics or for extensive medical treatments involving silver — can cause argyria, condition in which the skin turns grayish-blue. Brown researchers have discovered how that happens.  The process is similar to developing black-and-white photographs, and it's not just the silver.

PROVIDENCE, R.I. [Brown University] — Researchers from Brown University have shown for the first time how ingesting too much silver can cause argyria, a rare condition in which patients’ skin turns a striking shade of grayish blue.

“It’s the first conceptual model giving the whole picture of how one develops this condition,” said Robert Hurt, professor of engineering at Brown and part of the research team. “What’s interesting here is that the particles someone ingests aren’t the particles that ultimately cause the disorder.”

Scientists have known for years argyria had something to do with silver. The condition has been documented in people who (ill advisedly) drink antimicrobial health tonics containing silver nanoparticles and in people who have had extensive medical treatments involving silver. Tissue samples from patients showed silver particles actually lodged deep in the skin, but it wasn’t clear how they got there.

As it turns out, argyria is caused by a complex series of chemical reactions, Hurt said. His paper on the subject, authored with Brown colleagues Jingyu Liu, Zhongying Wang, Frances Liu, and Agnes Kane, is published in the journal ACS Nano.

Robert Hurt

"The particles someone ingests 

aren't the particals that ultimately 

cause the disorders"

Hurt and his team show that nanosilver is broken down in the stomach, absorbed into the bloodstream as a salt and finally deposited in the skin, where exposure to light turns the salt back into elemental silver and creates the telltale bluish hue. That final stage, oddly, involves the same photochemical reaction used to develop black-and-white photographs.

From silver to salt and back again

Hurt and his team have been studying the environmental impact of silver, specifically silver nanoparticles, for years. They’ve found that nanosilver tends to corrode in acidic environments, giving off charged ions — silver salts — that can be toxic in large amounts. Hurt’s graduate student, Jingyu Liu (now a postdoctoral fellow at the National Institute of Standards and Technology), thought those same toxic ions might also be produced when silver enters the body, and could play a role in argyria.

To find out, the researchers mixed a series chemical treatments that could simulate what might happen to silver inside the body. One treatment simulated the acidic environment in the gastrointestinal tract; one mimicked the protein content of the bloodstream; and a collagen gel replicated the base membranes of the skin.

They found that nanosilver corrodes in stomach acid in much the same way it does in other acidic environments. Corrosion strips silver atoms of electrons, forming positively charged silver salt ions. Those ions can easily be taken into the bloodstream through channels that absorb other types of salt. That’s a crucial step, Hurt said. Silver metal particles themselves aren’t terribly likely to make it from the GI tract to the blood, but when they’re transformed into a salt, they’re ushered right through.

From there, Hurt and his team showed that silver ions bind easily with sulfur present in blood proteins, which would give them a free ride through the bloodstream. Some of those ions would eventually end up in the skin, where they’d be exposed to light.

To re-create this end stage, the researchers shined ultraviolet light on collagen gel containing silver ions. The light caused electrons from the surrounding materials to jump onto the unstable ions, returning them to their original state — elemental silver. This final reaction is ultimately what turns patients’ skin blue. The photoreaction is similar to the way silver is used in black and white photography. When exposed to light, silver salts on a photographic film reduce to elemental silver and darken, creating an image.

Implications for nanosilver

Despite its potential toxicity, silver has been valued for centuries for its ability to kill germs, which is why silver nanoparticles are used today in everything from food packaging to bandages. There are concerns however that this nanoparticle form of silver might pose a unique health threat all its own.

This research, however, “would be one piece of evidence that you could treat nanoparticles in the same way as other forms of silver,” Hurt says.

That’s because the bioavailable form of silver — the form that is absorbed into the bloodstream — is the silver salt that’s made in the stomach. Any elemental silver that’s ingested is just the raw material to make that bioavailable salt. So ingesting silver in any form, be it nano or not, would have basically the same effect, Hurt said.

“The concern in this case is the total dose of silver, not what form it’s in,” Hurt said. “This study implies that silver nanoparticles will be less toxic than an equivalent amount of silver salt, at least in this exposure scenario.”

The National Science Foundation and the Superfund Research Program of the National Institute of Environmental Health Sciences funded the research.

$2.4 Million awarded to extend delayed cord-clamping study for full-term babies. Study involves URI, Women & Infants, and Brown's Advanced Baby Imaging Laboratory

KINGSTON, R.I. – October 4, 2012 – University of Rhode Island Professor of Nursing Judith S. Mercer, already knows from her earlier work that delaying the clamping of pre-term babies’ umbilical cords results in better overall health for the babies.

Now, the National Institutes of Health wants her to find out if doing the same for full-term babies will result in health benefits as well. The national health agency has awarded Mercer a five-year, $2.4 million grant to continue her work. The research project, known as the Infant Brain Study, also recently received a $100,000 grant from the Bill & Melinda Gates Foundation.

Mercer and her research team will study 128 infants from birth to 24 months to measure the effect of placental transfusion on the structure and functioning of the developing brain.

Debra Erickson-Owens, a co-principal investigator, and certified nurse midwife, said about one-third of the blood is left in the placenta if the cord is clamped immediately.

“The difference between delayed cord clamping and immediate clamping is 60 to 80 milliters of blood or 12 blood tubes (the tubes one sees when blood is drawn in a lab).” Erickson-Owens said. “That means with immediate clamping the babies receive less blood meant to be used in the earliest stages of development.”

The NIH grant comes just three-and-half years after the agency awarded Mercer a $2 million, five-year grant to expand her investigation into the benefits of delaying umbilical cord clamping for pre-term infants. She and her research team are now compiling data and findings from that research.

A pilot study showed strong evidence that delaying cord clamping allows the pre-term infant to absorb essential nutrients that help ward off infection and bleeding in the brain. In the pilot and

expanded nationally funded study, babies born pre-term had their cord clamping delayed 30 to 45 seconds.

In the new study, Mercer and her team want to find out whether delaying umbilical cord clamping for full-term infants by five minutes allows the placenta to transfer iron-rich blood cells to the newborn, reducing iron deficiency and anemia in the baby’s first year. She also wants to determine if delayed clamping enhances myelination in the brain, which is a process that requires iron to form a myelin sheath around a nerve allowing impulses to move more quickly. It leads to more complex brain processes and is critical to a healthy nervous system.

As with past studies, Mercer is working closely with Women & Infants Hospital, and she and Erickson-Owens are teaming up with Sean C.L. Deoni, director of the Advanced Baby Imaging Laboratory at Brown University.

Mercer, also a certified nurse midwife, said the delay time has been increased from the 30 to 45 second range for pre-term babies to five minutes for full-term babies for two main reasons: full-term babies do not usually need immediate and sometimes lifesaving interventions, and it allows a full placental transfusion when a baby is held skin-to-skin on its mother.

“We have been hoping for years to expand our research to full-term, healthy babies, but we needed a strong evaluation tool,” Mercer said.

That tool is magnetic resonance imaging (MRI) to chart each baby’s brain development, which will be provided by Deoni at Brown’s Advanced Baby Imaging Laboratory.

“Dr. Deoni is the first in the world to examine newborn brain development using MRI,” Mercer said. “If delayed cord clamping is shown to benefit all infants, then this new model of obstetrical care will go global.”

Current obstetrical practice at birth in the United States calls for cutting the infant’s umbilical cord immediately.

When immediate clamping occurs, 20 to 40 percent of the fetal-placental blood volume is left behind, according to the researchers. The blood contains enough iron-rich red cells to meet the infant’s iron needs for the first four to six months of life. Delaying clamping has been shown to increase the amount of iron in the blood without leading to any adverse effects for the infant.

Blood infused with iron is essential to long-term neurologic health, while iron deficiency in infancy adversely affects cognitive, motor, socio-emotional and behavioral development.

Babies participating in the study will be examined at birth, four months, 10 months and two years to assess their brains’ development.

“Delaying just a few minutes doesn’t cost anything,” Erickson-Owens said. “And while the baby is on the mother’s abdomen, skin-to-skin, the placenta can continue to support the baby while he or she gets used to the new environment.”

Participants must be 18 years of age or older, at least 30 weeks pregnant, have a healthy pregnancy, plan to breastfeed, and plan to deliver at Women & Infants Hospital.  For more information, visit http://www.womenandinfants.org/infantbrainstudy/

Professor John Donoghue named to The Institute of Medicine

The Institute of Medicine, one of the National Academies of Science, announced today that John Donoghue, the Henry Merritt Wriston Professor of Neuroscience and Engineering, has been elected as a member. 

“I am honored to receive this high recognition and to become part of an organization so dedicated to advancing progress in science, medicine and health care,” said Donoghue, who joins four other Brown colleagues as active members of the IOM. 

Donoghue directs the Brown Institute for Brain Science. He also pioneered and co-leads research on BrainGate, an investigational brain-computer interface now in clinical trials that is designed to help people with severe paralysis regain the ability to communicate and control their environment. In all, the IOM named 70 new members and 10 foreign associates this year. “Through their research, teaching, clinical work, and other contributions, these distinguished individuals have inspired and served as role models to others,” said IOM President Harvey V.Fineberg.

Five Questions With: Parker Wells, founder of Overhead.fm

Wells, who graduated from Brown in May with a degree in mechanical engineering, talked to Providence Business News about his triumph at the R.I. Business Plan Competition and his experience launching a technology startup.

PBN: Can you tell us a little bit about Overhead.fm and how it works?

WELLS: Overhead.fm is a streaming background music service. We have created an online music service like Pandora or Spotify, but our music is licensed to be played in public spaces like coffee shops, restaurants, doctors offices. This means that any storeowner can subscribe to our service and play music over any computer, tablet or smartphone. We have organized music into business-friendly commercial-free playlists, so you can quickly gain access to the right sound for your store without having to worry about the complicated world of music licensing.

PBN: Since winning the student track of the R.I. Biz Plan Competition, you moved on to StartEngine, an Los Angeles-based startup accelerator, how has that been going for you?

WELLS: Getting our start with the Rhode Island Business Plan Competition was an unbelievable boost for Overhead.fm. It gave us the ability to focus on building a company full-time and gave our business model the initial validation it needed to get into a selective accelerator program like StartEngine. The program itself has been invaluable in making connections in the music industry and meeting California tech investors. Thanks to a lot of support from the RIBPC and StartEngine we have built our music service, signed licensing agreements for musical performance rights, and have started acquiring customers. Moving from concept to sales in three months has already been an amazing experience and we are picking up momentum.

PBN: Do you plan to come back to Providence or are you staying on the west coast?

WELLS: We are definitely excited about moving back to Providence. The startup culture in Rhode Island is currently going through a renaissance. One of the country’s best and most established accelerators, Betaspring, continues to attract some of the best startups from around the country to our little state. Brown University, our alma mater, is also transforming its entrepreneurship program. The new Business, Entrepreneurship, and Organizations concentration is focused on new ventures, giving technology startups even more support than we have already had. We have made some great connections on the west coast and will continue participate fully in their startup-focused culture during our early funding stages. Providence provides the community that young founders truly benefit from.

PBN: What has been your favorite part of your tech startup experience?

WELLS: This is a tricky question. The best part of being a young entrepreneur is being able to meet and learn from remarkable people. While building this company I been given the opportunity to meet many founders and executives from the most influential tech, music, and entertainment companies. I have also been able to work alongside inspiring entrepreneurs and watch them navigate the many hurdles we all face. There are so many great entrepreneurs and executives out there who are also just really nice people and are willing to sit down and share their experiences.

PBN: What advice do you have for other college students or young people looking to form their own technology startup?

WELLS: I recommend going for it. This is a great time to start a technology startup. As far as advice goes, I would say that the most important thing is the team you work with. If your team is dedicated, skilled, and works well together, you can overcome a lot of challenges.

By Emily Greenhalgh

Providence Business News

Grant for Chemical Innovation Center

Researchers at Brown have been awarded $1.75 million to explore the potential of using carbon dioxide instead of fossil fuels in the production of common industrial chemicals. Advances could reduce the chemical industry’s carbon footprint and help stabilize production costs in the face of ever increasing fuel prices. 

“The goal is to find new ways to produce some of the world’s largest-volume chemicals from a sustainable carbon source that the earth not only has in excess but urgently needs to reduce,” said Tayhas Palmore, professor of engineering and principal investigator on the grant.

The funding comes from the National Science Foundation’s Centers for Chemical Innovation Program. The research team includes Wesley Bernskoetter, Christoph Rose-Petruck, Dwight Sweigart, and Shouheng Sun from the Department of Chemistry, as well as Robert Hurt and Andrew Peterson from the School of Engineering and Nilay Hazari from the Department of Chemistry at Yale. The team is administered by Brown’s Institute for Molecular and Nanoscale Innovation (IMNI).

Brown School of Engineering Hosts NEW.Mech Workshop

The Brown University School of Engineering is hosting the 2012 New England Workshop on the Mechanics of Materials and Structures on November 3, 2012, at the Granoff Center.

The one-day workshop aims to bring together the New England Mechanics community with an interest in exploring new directions on the mechanics of materials and structures and sharing the latest advancements in the field. The workshop is free of charge, and is focused primarily around students (graduate and undergraduate) and postdocs. The previous two years have seen tremendous enthusiasm and excitement from the scientific community and Brown is excited to be this year’s host.

The workshop will consist of four plenary invited talks and a number of contributed short talks. There will also be a poster competition, and the workshop will include a new component, the “Gallery of Mechanics”. This event will include movies that display research in the New England mechanics community. There will be awards for the top three entries.

The workshop is being organized locally by Christian Franck and Shreyas Mandre, assistant professors of engineering at Brown.

For more information, please go to: http://www.brown.edu/conferences/new-england-mechanics-materials-structures/

Professor Nitin Padture Named Editor of Scripta Materialia

Brown University School of Engineering Professor Nitin Padture has been named editor of Scripta Materialia, one of the leading journals in the field of materials science and engineering. In this role, Padture will serve a four-year term and will handle approximately 300 manuscripts per year.

“It is a great opportunity to contribute toward the shaping of a fast moving field, and I am humbled by the honor,” said Padture.

Padture, Professor of Engineering and Director of the Center for Advanced Materials Research (CAMR) at Brown, joined the Brown faculty in January of 2012. Previously he was College of Engineering Distinguished Professor at The Ohio State University, and also the founding director of the NSF-funded Materials Research Science and Engineering Center (MRSEC) at OSU.

Padture received B.Tech. in metallurgical engineering from Indian Institute of Technology, Bombay (1985), M.S. in ceramic engineering from Alfred University (1987), and Ph.D. in materials science and engineering from Lehigh University (1991).

He was a postdoctoral fellow at the National Institute of Standards and Technology (NIST) for three years, before joining the University of Connecticut faculty in January 1995 as an assistant professor. He became an associate professor in 1998 and was promoted to professor in 2003. He served as interim department head at UConn before moving to Ohio State in January 2005.

Padture’s teaching and research interests are in the broad areas of synthesis/processing and properties of advanced materials used in applications ranging from jet engines to computer chips, impacting transportation, energy, and information technology sectors. Specifically, he has active research in tailoring of structural ceramic composites and coatings, and functional nanomaterials including graphene and perovskites.

Padture has published over 125 journal papers, which have been cited over 5,000 times. Padture is a co-inventor of four patents, and he has delivered some 150 invited/keynote/plenary talks in the U.S. and abroad. A fellow of the American Ceramic Society, he has received that society’s Roland B. Snow, Robert L. Coble, and Richard M. Fulrath awards. Padture is also a recipient of the Office of Naval Research Young Investigator Award, and he is a Fellow of the American Association for the Advancement of Science. Previously, Padture served as a principal editor of Journal of Materials Research and an associate editor of Journal of the American Ceramic Society.

Brown to lead multi-university quantum metamaterials research

Through a new Multidisciplinary University Research Initiative (MURI) awarded by the Air Force Office of Scientific Research, Brown will lead an effort to study new optical materials and their interactions with light at the quantum scale. The initiative, which includes six other top universities, will receive $4.5 million over three years, with a possible two-year extension.

Harnessing the power of light at the quantum scale could clear the way for superfast optical microprocessors, high-capacity optical memory, securely encrypted communication, and untold other technologies. But before any of these potential applications sees the light of day, substantial obstacles must be overcome — not the least of which is the fact that the wavelength of light is larger than quantum-scale objects, limiting the range of possible light-matter interactions.

Rashid Zia
"This program will bring together ten groups and 40-plus
researchers... to help answer questions that we couldn't
have imagined a short time ago. We are very optimistic
about where this will lead."

Rashid Zia, the Manning Assistant Professor of Engineering, will lead the team in addressing these challenges. He spoke recently with science writer Kevin Stacey.

What are you hoping to accomplish with this MURI?
We’re trying to help define an emerging field. The title of the MURI is “Quantum Metaphotonics and Quantum Metamaterials.” Ultimately what we’re trying to do is expand the range of materials and light-matter interactions available for quantum optics.

The field of metamaterials has already expanded the range of optical materials and phenomena available at larger, classical scales. People are doing things with metamaterials that we couldn’t have imagined before. For example, researchers are making metamaterials with negative refractive indices, which can literally bend light backward around objects. Others have used metamaterials to make lenses that can image things smaller than the diffraction limit of traditional lenses. What we’re doing now is asking what happens when we bring these metamaterials down to the scale of quantum emitters — the level of things that can emit a single photon at a time.

Can you talk a bit about the challenges involved in doing this?
When you talk about the way light interacts with matter at the quantum level, the types of interactions and the strength of those interactions are limited by a size mismatch. The optical wavelength is something like 100 times larger than a quantum emitter. For example, a quantum dot — a small bit of semiconductor we can use as a light emitter — is 5 to 10 nanometers. The wavelength of light is on the order of 500 to 1,000 nanometers. The problem is that the quantum dot doesn’t know there’s a wave. It can’t see the spatial variation of the light wave, just its local variation in time. So we need to shrink the wavelength of light to increase our interactions. Or we might increase the wavelength to collectively interact with many quantum emitters. And hopefully we can learn something fundamental about the nature of light that opens up new ways of manipulating these interactions. Those are the types of things we’ll be addressing.

In quantum optics we’re limited in part by the kinds of materials we can use. One of the common materials for quantum optics today is the nitrogen vacancy defect in diamond, so-called diamond NV centers. As you can imagine, diamond is not the cheapest or most scalable technology. The challenge posed for us is how to use the semiconductor materials we use for electronics and extend their optical properties with metamaterial designs, so we can perform quantum optics at wavelengths and with materials commonly used in telecommunications today.

How does the research you’re doing in your lab at Brown fit in?
It’s usually assumed that all light-matter interactions at visible frequencies result from the push-pull forces exerted by electric fields. These are called electric dipole transitions. One of the things we do in my lab is study things that aren’t electric dipoles — for example, magnetic dipoles. Because of the size mismatch we just discussed, it’s often assumed that magnetic dipole transitions are around 100,000 times less likely to happen than electric dipole transitions. In other words, it’s assumed that light emission from magnetic dipoles simply doesn’t happen. But the fact is we see magnetic dipole emission every day from the lanthanide ions that are commonly found in fluorescent lights. What we’ve been able to do is quantify the magnetic nature of light.

We just published a paper on this in Nature Communications. Basically, we demonstrated a way to tell how light was emitted, and rather than simply counting the number of photons a system generates, we can tell you which fraction of them came from electric dipoles and which fraction came from magnetic dipoles. This helps us understand fundamental properties about quantum emitters, the source of this light. It might also help us access higher-order light-matter interactions, enabling new ways to modulate light or to trap energy in optical excitations and get it out when you want, which could be useful for things like optical memory.

Who else is involved in this work?
The team includes people who are world-class experts in different areas. Nader Engheta at Penn, Nicholas Fang at MIT, and Xiang Zhang at UC–Berkeley are experts in metamaterials. Harry Atwater at CalTech and Mark Brongersma at Stanford are experts in plasmonics, which is the science of using metal structures to enhance light-matter interactions. Shanhui Fan and Jelena Vuckovic at Stanford are experts in quantum optics. Seth Bank at UT–Austin and Arto Nurmikko and me here at Brown, work on quantum emitters.

It’s really an exciting project. Over the next five years, this program will bring together 10 groups and 40-plus researchers with complementary expertise to help answer questions that we couldn’t have imagined a short time ago. We are very optimistic about where this will lead.