Shreyas Mandre wins HFSP grant

Shreyas Mandre, assistant professor of engineering, is part of an international research team awarded a Young Investigator Grant by the Human Frontier Science Program. The team will receive $350,000 in each of three years to study the mechanics of the human foot.

“Understanding the fundamental mechanics of the foot informs the fields of biotechnology, robotics and
human evolutionary biology,” Mandre said. “Our research in this field considers the interaction of the foot with uneven ground to investigate how humans maintain a stable running gait. The interdisciplinary and international nature of this research falls squarely within HFSP purview.”

The research is led by Madhusudhan Venkadesan, a biomechanician from the National Center for Biological Sciences in India, and in collaboration with Mahesh Bandi, a physicist at Japan’s Okinawa Institute of Science and Technology. The researchers hope to shed light on evolution of bipedalism, a task possible only by combining the capabilities of the three team members.

“The goal of my lab is to develop simple but quantitatively accurate descriptions of phenomena with applications to energy, environment and biology,” Mandre said. “We welcome interdisciplinary collaboration with other groups and actively seek talented undergraduate, graduate and postdoctoral researchers.”

“The interdisciplinary and international nature of this research overlaps perfectly with the research mission of the School of Engineering and Brown University,” said Larry Larson, dean of the School of Engineering.

Based in Strasbourg, France, the Human Frontier Science Program aims to promote basic research in the life sciences by funding researchers all over the world. This year, the organization awarded $34 million to 33 research teams that include scientists from 26 countries.

Could lubricin stop OA in damaged joints?

Researchers from Brown and Rhode Island Hospital have shown that joint fluid lacking in a protein called lubricin fails to adequately lubricate joints. That lack of lubrication leads to increased friction in the joint and eventually to the death of cartilage cells. The work also shows that lubricin protects cartilage and could serve as a means to reduce the risk or even prevent osteoarthritis.

“We’re saying it’s worth 

investigating the use of lubricin 

in damaged joints before onset 

of osteoarthritis.”

Dr. Gregory Jay

Researchers from Rhode Island Hospital and Brown’s School of Engineering have shown in two different animal models that joint fluid lacking in a protein called lubricin fails to adequately lubricate joints. That lack of lubrication leads to increased friction in the joint and eventually to the death of cartilage cells, the research found. The findings, published in the Proceedings of the National Academy of Sciences, help to confirm something researchers have long thought about the root cause of osteoarthritis — that increased friction destroys cartilage, causing joints to fail. Importantly, the work also shows that lubricin protects cartilage and could serve as a means to reduce the risk or even prevent osteoarthritis.

Dr. Gregory Jay, of the Department of Emergency Medicine at Rhode Island Hospital and the School of Engineering at Brown, led the study. He talked with Kevin Stacey about the new findings.

Could you summarize what exactly the research found?

We were able to show experimentally in joints explanted from mice and cows that friction between rubbing cartilage surfaces under a physiologic load is responsible for apoptosis, or programmed cell death of the cells that make up cartilage. Importantly, we found that cell death can be mitigated by the presence of a joint protein called lubricin. Previous studies had reported that lubricin could reduce friction in joints, but none had shown that lubricin played a direct role in protecting cartilage cells.

Cartilage is a mechanical material. It’s meant to absorb strain, to be compressed, and to withstand very high loads. A typical joint can withstand 2,000 pounds per square inch easily. And yet if you overstrain it or if intervening lubricin is not present between cartilage surfaces, then the cells underneath the surface will experience excessive strain — and we show that as a result they undergo programmed cell death.

What do those findings tell us about the role of injury in osteoarthritis?

The findings suggest a mechanism by which major injury or repeated minor injuries to joints can cause osteoarthritis. We know that inflammation and injuries — meniscal tears, ACL tears, gout, inflammatory joint conditions — all down-regulate lubricin. We also know that injuries are an epidemiologic risk factor for OA. So our findings suggest that the loss of lubrication due to the down-regulation of lubricin after injury may be a causal link in the etiology of OA. Once you cause that down-regulation in lubricin, you’re creating a vulnerable period for articular cartilage, we believe.

Are there any potential clinical implications to this?

It would seem to make sense to try to restore lubricin in the period just after an injury to help protect the cartilage and possibly to lessen the prospects for developing OA later in life. Doctors currently inject hyaluronic acid — the viscous component of joint fluid — as part of a therapy called viscosupplementation. But this is generally performed in patients with advanced disease and doesn’t include lubricin. We’re saying it’s worth investigating the use of lubricin in damaged joints before onset of OA.

This study involved both medical researchers and bioengineers. How did those two perspectives inform the work?

This was a collaborative effort between the Departments of Emergency Medicine and Orthopaedics at Rhode Island Hospital and the School of Engineering at Brown.

Like many examples of translational medical research, the work is multidisciplinary and occurs where different fields intersect. Engineers were needed to develop joint pendulum measurement systems ex vivo and measures of cartilage friction in vitro. There was also innovation in testing for biological markers after mechanical testing was done.

What’s the next step for this line of research?

Similar work will be carried out in a large animal model as we work toward a possible orphan drug indication study in patients afflicted with CACP syndrome, a condition in which patients lack lubricin entirely. This will be possible once lubricin is manufactured and can be introduced into joints at risk.

Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews, and maintains an ISDN line for radio interviews. For more information, call (401) 863-2476.

On a Mission

The bombs didn’t stop, not even on Christmas night, when they fell less than two miles away. At Mother of Mercy Hospital in the village of Gidel in Sudan’s Nuba Mountains, Christian missionary Tom Catena ’86 kept working. As the only medical doctor at the only hospital in the entire region, he had little choice.

Tom Catena '86

A war over oil had broken out in 2011 between Sudan and South Sudan, and Catena found himself in the middle of it. “When the fighting started, almost all of the expatriates that were here left,” Catena says. “For me, I think the initial thought was that in good conscience I can’t leave the hospital. I was the only doctor here. I’m still the only doctor, pretty much for all of the Nuba Mountains. For me, it was fairly simple. I could not live with myself if I just packed up and left the place and left all the people here in that situation.”

During the evacuation, Catena’s nurse anesthetist left. So did his lab technician and pharmacist. “Anybody that had any training was taking off,” Catena says. “I thought, ‘Let me just stay around, and I will do my best.’” Two nuns stayed behind to help him. Meanwhile victims from the bombings streamed to the hospital.

Catena, whom other doctors have praised as a modern-day Albert Schweitzer, praised the local Nuba people, who helped to pick up the slack. Although they had little formal education, they became Catena’s nurses, assisting him as he performed surgery. He says he probably performs more than a thousand operations a year at the hospital. “People survived, much to our disbelief,” he says. “That gave us confidence, and we kept going.”

For Catena, who lives with his staff in a concrete building near the hospital, a typical day starts at 6:30 with morning Mass. He begins rounds at 7:30. The hospital has 300 beds, but sometimes there are so many patients they must sleep two or three to a bed. On some days there is no water; on others, no electricity. “You get worn out,” he says. “You get tired. You get frustrated.”

Catena remains on call throughout the night. With no administrative staff, he also uses the evenings to order supplies and keep patient records up-to-date. Despite the fatigue and the stress, he persists. “Some days are better than others,” he says. “I enjoy the work, but some days it is drudgery. Whether terrible things happen or whether we are in danger or there is no food, the idea is we are here to serve. It is as simple as that.”

Catena’s Christian faith was apparent even at Brown, where Campus Crusade for Christ director Kent Dahlberg was a mentor and spiritual teacher. A mechanical engineering concentrator, Catena excelled academically and was a Rhodes Scholar candidate. He was also a good athlete, an Associated Press honorable mention All-American football player and a first-team All-Ivy pick as a defensive lineman. As a senior in 1985, he helped the Brown defense post shutouts in four of its seven Ivy League contests. His nickname was Catman.

“Quite simply, he’s the nicest, most unselfish person I know,” says George Reilly ’87, Catena’s teammate and fraternity brother. “In college he was my spiritual mentor, my super-tough teammate, my big brother, my comic relief. He led a Bible study in our fraternity and always led by example. He walked the walk.”

Teammate Ted Moskala ’86 recalls that Catena was small for a defensive lineman. “But he was strong, and he was extremely quick,” he adds.

Against a powerful Rhode Island team, Catena sacked Ram quarterback Tom Ehrhardt for a safety to lead Brown to a 32–27 upset win. On senior day in his final home game, he registered three sacks as Brown blanked Columbia, 34–0. “If you could combine Mother Teresa and Mean Joe Greene,” says Reilly, “you’d get Catman. He makes us all want to be better people. I tell my three daughters stories about him because he epitomized what a student-athlete is all about.” The Ivy Football Association recognized Catena for his selflessness at its annual New York City dinner on February 7.

After Brown, Catena felt called to missionary work. Realizing that in the mid-1980s opportunities for someone with his training were limited, he decided to go to medical school at Duke on a U.S. Navy scholarship. “I’ve always had an interest in other people and cultures,” he says, “and I felt called to use my abilities to serve those people.”

It was during his fourth year at Duke that he went on his first mission to Kenya. If he had any doubts about what he wanted to do with the rest of his life, they vanished in Kenya. His two months there, he says, “sort of cemented my belief. For me it was such exciting work: you got to do all kinds of different things medically. You were dealing with a population that had very little access to health care. For me this was what medicine was about.”

After graduating, he completed his navy commitment and did a postgraduate residency in Indiana. “During that time I was, of course, still interested in doing mission work,” he says, “so I was looking for organizations that would sponsor doctors, and I came across the Catholic Medical Mission Board.”

He spent a month in Guyana, which was followed by another month in Honduras. When he finished his residency in 1999, he decided to continue volunteering with the Catholic Medical Mission Board and spent two years in rural Kenya at Mutoma Hospital. He then volunteered for the next six years at St. Mary’s Hospital in Nairobi before helping establish the Mother of Mercy Hospital in southern Sudan in 2007.

The hospital’s resources were strained from the start, as victims of fighting in Darfur and, later, central and southern Sudan arrived seeking medical care. Catena twice contracted malaria in the months after the hospital opened, and he lost fifty pounds.

Catena can’t imagine leaving the country. “I’d like to stay here long term, God willing,” he says, “although I realize that this place is unstable and the situation could change any day. My plan is to stay as long as it takes to make the hospital a stable institution.”

Does he ever fear for his life? “Yes, there have been times when I thought maybe the end was coming near,” Catena says. “Despite this, I think when it’s our time to leave this earth, it’s just our time to go and not to worry about it so much. Let me do what I can while I’m still here.”

Read more about Catena and Mother of Mercy Hospital at http://cmmb.org/supporting-mother-mercy-hospital

- by Gordon Morton
(This story originally appeared in the March/April edition of the Brown Alumni Magazine.)

Wei Yang to lead China’s National Natural Sciences Foundation

Wei Yang Ph.D.’85 Sc.D.’12 hon., an internationally celebrated engineer and materials science researcher, educator, and administrator, has been named president of China’s National Natural Sciences Foundation (NSFC), the nation’s top science agency. He takes the helm of an organization that last year allocated $2.8 billion to fund scientific activity. In a recent interview with Science magazine, Yang said he hopes to increase the agency’s funding substantially.

“China has to transition from an economic powerhouse to a technological powerhouse and then to a scientific and cultural powerhouse,” he said. “To achieve this goal, we will need many scientists, and we need to convince the government that it should provide more funding to the NSFC.”

Before the NSFC, Yang was president of Zhejiang University and head of the Chinese Academy of Sciences Technological Science Division. He was the youngest person ever to achieve the rank of full professor of engineering at Tsinghua University, which he did just four years after his graduation from Brown. Born in Beijing, Yang was educated in the United States and China (B.S., Northwestern Polytechnic University, 1976; M.S., Tsinghua University, 1981; Ph.D., Brown University, 1985).

In addition to continuing an active and very productive career as a research engineer in fracture mechanics, mechatronic reliability, and micro/nanomechanics (11 books and 211 technical papers in internationally refereed journals), Yang has served in a number of national and international positions as an educator and administrator. He became director of the Failure Mechanics Laboratory of the Chinese Ministry of Education in 1993. For seven years (1997–2004), he headed the Department of Engineering Mechanics at Tsinghua, also serving for a time as executive dean of the Aerospace School. From 2004 to 2006, he served as director-general of the Academic Degrees Committee of the State Council of China and also headed the Directorate of Graduate Education. He began as president of Zhejiang University, one of China’s largest and oldest universities, in 2006.

As head of the Chinese Academy of Sciences Technological Science Division, Yang has had extensive international scientific experience. He has served as regional editor for several journals in the field of composite materials and has been on the editorial boards of the International Journal of Fracture, Fatigue & Fracture of Engineering Materials & Structures, and the Archive of Applied Mechanics, among several others.

Early in 2009, Yang became widely known for a stern and dedicated fight against scientific misconduct, dealing strictly with researchers found to have engaged in misconduct and proactively developing training programs to support scientific integrity. Organizations and journals,Nature among them, praised his zero tolerance policies.

Yang has supported and worked for collaborations with universities in the United States, Germany, the Netherlands, Singapore and elsewhere. His own postgraduate students — more than 40 of them — have extended his international reach. More than 10 of them hold engineering faculty positions in the United States and Europe. He has been honored extensively for his efforts, including the 2009 Brown University Engineering Alumni Medal (BEAM).

New technique could improve optical devices

Understanding the source and orientation of light in light-emitting thin films — now possible with energy-momentum spectroscopy — could lead to better LEDs, solar cells, and other devices that use layered nanomaterials.

PROVIDENCE, R.I. [Brown University] — A multi-university research team has used a new spectroscopic method to gain a key insight into how light is emitted from layered nanomaterials and other thin films.

The orientation of light emission
The angular distribution of light emission from monolayer

MoS₂, left, closely matches the theoretical calculations for
in-plane oriented emitters, right, indicating that light
emission from MoS₂ originates from in-plane oriented
emitters. Credit: Zia lab/Brown University

The technique, called energy-momentum spectroscopy, enables researchers to look at the light emerging from a thin film and determine whether it is coming from emitters oriented along the plane of the film or from emitters oriented perpendicular to the film. Knowing the orientations of emitters could help engineers make better use of thin-film materials in optical devices like LEDs or solar cells.

The research, published online on March 3 in Nature Nanotechnology, was a collaborative effort of Brown University, Case Western Reserve University, Columbia University, and the University of California–Santa Barbara.

The new technique takes advantage of a fundamental property of thin films: interference. Interference effects can be seen in the rainbow colors visible on the surface of soap bubbles or oil slicks. Scientists can analyze how light constructively and destructively interferes at different angles to draw conclusions about the film itself — how thick it is, for example. This new technique takes that kind of analysis one step further for light-emitting thin films.

“The key difference in our technique is we’re looking at the energy as well as the angle and polarization at which light is emitted,” said Rashid Zia, assistant professor of engineering at Brown University and one of the study’s lead authors. “We can relate these different angles to distinct orientations of emitters in the film. At some angles and polarizations, we see only the light emission from in-plane emitters, while at other angles and polarizations we see only light originating from out-of-plane emitters.”

The researchers demonstrated their technique on two important thin-film materials, molybdenum disulfide (MoS2) and PTCDA. Each represents a class of materials that shows promise for optical applications. MoS2 is a two-dimensional material similar to graphene, and PTCDA is an organic semiconductor. The research showed that light emission from MoS2 occurs only from in-plane emitters. In PTCDA, light comes from two distinct species of emitters, one in-plane and one out-of-plane.

Rashid Zia
"If you were making an LED using these layered materials
and you knew that the electronic excitations were
happening across an interface, then there's a specific way
you want to design the structure to get all of that light out
and increase its overall efficiency."

Once the orientation of the emitters is known, Zia says, it may be possible to design structured devices that maximize those directional properties. In most applications, thin-film materials are layered on top of each other. The orientations of emitters in each layer indicate whether electronic excitations are happening within each layer or across layers, and that has implications for how such a device should be configured.

“If you were making an LED using these layered materials and you knew that the electronic excitations were happening across an interface,” Zia said, “then there’s a specific way you want to design the structure to get all of that light out and increase its overall efficiency.”

The same concept could apply to light-absorbing devices like solar cells. By understanding how the electronic excitations happen in the material, it could be possible to structure it in a way that coverts more incoming light to electricity.

“One of the exciting things about this research is how it brought together people with different expertise,” Zia said. “Our group’s expertise at Brown is in developing new forms of spectroscopy and studying the electronic origin of light emission. The Kymissis group at Columbia has a great deal of expertise in organic semiconductors, and the Shan group at Case Western has a great deal of expertise in layered nanomaterials. Jon Schuller, the study’s first author, did a great job in bringing all this expertise together. Jon was a visiting scientist here at Brown, a postdoctoral fellow in the Energy Frontier Research Center at Columbia, and is now a professor at UCSB.”

Other authors on the paper were Sinan Karaveli (Brown), Theanne Schiros (Columbia), Keliang He (Case Western), Shyuan Yang (Columbia), Ioannis Kymissis (Columbia) and Jie Shan (Case Western). Funding for the work was provided by the Air Force Office of Scientific Research, the Department of Energy, the National Science Foundation, and the Nanoelectronic Research Initiative of the Semiconductor Research Corporation.

by Kevin Stacey