Amber Doiron, assistant professor of bioengineering, says current methods of assessing atherosclerosis — commonly known as hardening of the arteries — are not terribly accurate. Some 30 percent of deaths worldwide can be attributed to the disease, which occurs when fat, cholesterol and other particles form hard structures called plaques in the walls of arteries.

“It’s really a guessing game right now,” she says. “Doctors use factors like blood pressure and cholesterol level to get an idea of a patient’s risk. Then they use plaque size as a general measure of whether a person has the disease. But there’s a fairly poor correlation between plaque size and heart attack or stroke.”

Doiron, who has an interest in molecular imaging as well as expertise in nanoscience, wants to help physicians do a better job of identifying which plaques are cause for concern.

She and a Temple University colleague recently received a two-year, $418,000 grant from the National Institute of Biomedical Imaging and Bioengineering to support this project. It’s a notable success in part because this was Doiron’s first National Institutes of Health grant proposal.

The researchers will use a combination of polymers and superparamagnetic iron oxide nanoparticles for the study. The nanoparticle is sensitive to oxidative stress, which occurs in atherosclerosis and has been linked to patients who have a higher prevalence of heart attack and stroke. Using an MRI scan, the researchers will be able to see how active the nanoparticle is, which will indicate whether the plaque is stable.

“A stroke or a heart attack doesn’t necessarily come when a plaque fully blocks the flow of blood through an artery,” Doiron explains. “What happens is the plaque ruptures and the gunk that underlies the plaque is exposed to blood and a clot forms. The clot builds quickly — on an hour time scale as opposed to over years — and the clot can grow there until it blocks flow, or it can dislodge and block flow somewhere else. Most heart attacks do not occur from a full blockage of plaque. It happens because the plaque bursts. Same thing with strokes. That’s why size isn’t necessarily indicative of how dangerous a plaque is.”

The discovery of a molecule or a cell type that indicated which plaques are safe and which ones are dangerous would be a huge breakthrough, Doiron says. She thinks oxidative stress may be such an indicator.

“Atherosclerosis is an incredibly complex disease that progresses over decades,” Doiron says. “It’s hard to tell who’s walking around with plaques that are stable, relatively safe, and who has plaques that may cause a heart attack tomorrow. For some patients, the first sign of trouble is a heart attack.”

Medications like the insulin she has injected every day since she was 16.

Now, as a biochemistry and neuroscience major at Binghamton University, she’s taking the first steps: helping to understand how nanoparticles can improve rechargeable batteries.

There’s no disconnect here: The skills and knowledge she’ll acquire working on Assistant Professor Gretchen Mahler’s project can be taken in many directions.

The connection, MacAneney said, is this: Industry leaders are interested in using nanoparticles of vanadium oxide as a cathode in rechargeable lithium ion batteries. “But before they can use nanoparticles in batteries, they need to understand the health effects,” she said, both on production workers making the products and the everyday user.

Vanadium in various forms can help lithium batteries store more energy, discharge more power and recharge faster — perfect for any number of smart energy projects from hybrid-electric or all-electric vehicles to household energy storage.

That is, if it doesn’t harm people. Acute vanadium oxide exposure in its larger form has been linked to increased bronchial infections, pneumonia, inflamed tissues and irritated eyes, throat, lungs and nasal tissue — even nervous disorders and paralysis. The health effects of vanadium oxide nanoparticles have never been studied.

“Our hypothesis is that when these nanoparticles come in contact with epithelial cells, it’ll cause inflammation and absorption,” MacAneney said.

The data will help Mahler and a colleague at the State University of New York at Potsdam to prepare a proposal for grant funding. And it’s a good project to help put a new researcher through her paces, using newly acquired skills from eight weeks of lab training.

“I put them through a pretty rigorous training program,” Mahler said. It weeds out people unsuited to a life of research and keeps the new researcher and her colleagues safe. “She is just starting to dive into the nanoparticle work.”

But understanding how a body can absorb nanoparticles relates directly to McAneney’s interest in medication. Insulin today cannot easily survive gastric acids, making oral insulin impractical.

“But can you encapsulate it in something to protect it?” she asked. “It wouldn’t degrade in the stomach.”

Interesting question, and one McAneney plans to keep asking on her way to a doctorate and perhaps a medical degree, too.

Binghamton junior Yudi Pardo works on one of the first hurdles: taking the photosynthetic engine out of a plant cell and putting it somewhere it can be used. It’s a problem he has been examining for nearly five years — since before he received his high school diploma.

Now, as a bioengineering major working in Assistant Professor Gretchen Mahler’s laboratory, he’s taking advantage of his opportunities.

He’s working with cyanobacteria ― essentially a blue-green algae — seeking a way to harvest its photosynthetic thylakoids. “How do I extract the complexes in a way where they won’t degrade over time?” he asks.

The solution, eventually, is to graft the thylakoids, which reside in the cell’s inner membrane, onto the cell’s outer membrane. “So when the outer membrane flakes off, you have a working photo system,” he says. “There’s a lot of genetic manipulation.”

Mahler sometimes has difficulty mentoring him, because bio-energy isn’t her research focus. “A lot of students don’t realize they’re into research so early,” Mahler says, much less develop such a specific interest. “He came to me with the project.”

“It’s an interesting problem,” she says, “That’s a good area of research. Nobody has done it.”

It’s an area of research with useful implications. Nathan Nelson of the University of Tel Aviv has developed an ultra-small working solar cell based on a pea plant; it generates 10 volts and with 20 percent efficiency is moderately more efficient than current silicon-based cells.

Nelson and Pardo understand some parts of a plant’s photosynthetic engine are 95 percent to nearly 100 percent efficient. If those parts can be harnessed properly, it could lead to great advances in bio-solar cell efficiency — enough to make them cost effective.

“If we can bring that to the entire device, that would make solar technology more viable for people,” Pardo says. “That really high efficiency on a small scale is what drew me in.”

Biological cells would be faster to construct and largely carbon neutral, although questions remain about how durable biological cells would be, and how they would distribute their energy.

But Pardo, who’s just 20 years old, has time to answer them. “I don’t know specifically where I want to go with this,” he says, citing interests in bio-medicine and medical instrumentation. “But alternative energy has always been at the top of my list.”

Ronald Miller, a junior majoring in bioengineering, has interned for two summers with Daniel Tso at SUNY Upstate Medical Center, working with specialized cameras to measure activity level in the human retina, a light-sensitive layer of tissue that lines the inner surface of the eye. “Over the summer I worked in a vision lab in Upstate Medical Center, and we’d image the retinas of different students and volunteers, and myself, too,” Miller says. “Right now we’re trying to quantify the signal and measure what it looks like consistently in a healthy person.”

Being able to measure signals in a healthy person, Miller says, could allow for easier and earlier detection of retinal abnormalities.

“We tried to quantify that signal in healthy individuals so we can see what indicates certain retinal diseases like retinitis pigmentosa, glaucoma and macular degeneration,” he says. “A lot of times you don’t know you have one of these conditions until you have really big vision deficits, and by then it’s really difficult to correct or treat.”

Miller uses a laser to stimulate the retina, shining the light for less than a second and then recording activity level for the following five seconds. The lasers allow Miller to use differently shaped stimuli and see the resulting effects on infrared images of the retina.

Miller also works with bioengineer Jacques Beaumont, a visiting professor at Upstate Medical University who was until recently a Binghamton faculty member. They plan to re-create and eventually improve on a model of the visual cortex initially developed at New York University.

“I want to try to improve upon the model that they created, make it more biologically accurate,” Miller explains. “Eventually, if the model is totally accurate, you could test the effects of various drugs.”

Beaumont and Miller plan to continue working together this summer, when Miller will have a chance to put his training to use on a software development project. “I expect a significant contribution when he will be able to run simulations in parallel with his experiments,” Beaumont says.

Beaumont says Miller is developing an expertise on vision. “I hope he will continue in his future career applying modeling and experiments to develop an understanding of the molecular mechanisms of various forms of blindness,” Beaumont says.

Miller, a Syracuse native, is also an event coordinator for the Student Volunteer Center on campus. “It’s fun, I get to meet people and it’s cool to see what’s around the community because a lot of people need help with events and students don’t know about it,” Miller says.

He plans to pursue a doctorate or medical degree. His grandfather, who was a pulmonary specialist, inspired him to enter the medical field.

“I want to pursue a career in medicine because I want to be able to improve people’s lives,” Miller says, “possibly by inventing a biomedical device or devising some form of early detection or treatment plan.”

Technology for the hearing-impaired is hardly perfect. The small microphones contained within hearing aids do a good job of boosting volume, but that can be a problem in a noisy restaurant as background sounds get boosted as much as your dinner date’s conversation. Miles used a tiny structure found in the ear of a fly, Ormia ochracea, as a model to develop the world’s smallest directional microphones.

His research received several million dollars in funding from the National Institutes of Health nearly a decade ago, but that money was focused on scientific discovery and not on the development of a commercial product. Last year, the Research Foundation for the State University of New York (RF) supported development of the technology with $50,000 from the SUNY Technology Accelerator Fund (TAF). Now, Miles has earned an additional $100,000 from the fund to develop his microphone in a market-strategic way. Binghamton University will match that $100,000, providing additional resources to advance this research.

“As part of the review process, the RF team did a marketing study to determine potential markets for licensing and commercialization,” Miles says. “We ended up modifying our design to improve the marketability of our technology. By using a more conventional sensing scheme, it should be easier to commercialize.”

“Dr. Miles’ work is a perfect example of the real-world impact of SUNY research,” says Timothy Killeen, president of the RF and SUNY vice chancellor for research. “Ground-breaking research is being conducted by SUNY faculty and students across New York State. Our job is to provide the support that facilitates the advancement of invention to produce commercially viable technologies that serve the public good and trigger entrepreneurial and economic opportunity. Congratulations to Dr. Miles and his Binghamton University team.”

The Research Foundation launched the TAF in April 2011 to support innovation across the SUNY research community and to provide proof-of-concept funding for SUNY’s most promising technologies. In its first year, the fund produced two licensing agreements and three startup companies.

The TAF also recently announced first-round funding for an additional six projects proposed by SUNY researchers. Proposals were evaluated by the TAF managing director with input from external experts. The technologies selected include advancements in areas ranging from antibiotics to suicide prevention. Binghamton University bioengineer Kenneth McLeod had one of the winning proposals, with a plan to develop a personalized heating system that is designed to save energy while allowing people to manage their weight by maintaining a consistent body heat balance.

“Smart” micro-environmental systems keep employees in heat balance in the typical office environment. An infra-red based system heats people inside rooms in a building rather than blindly heating all spaces equally, whether occupied or not. Individuals obtain the comfort level they desire, resulting in improved productivity and decreased building operational costs. This “green” technology would reduce the energy needed to operate buildings, which accounts for 45 percent of all energy use in the U.S.

An equally important aspect of “radiant people heating” is that it triggers weight loss, McLeod says. This secondary benefit may provide even larger economic benefits to employers, employees and society. Building operators, engineers and architects can deploy micro-environmental control technology systematically to increase the economic and energy sustainability of their projects — and keeping people in buildings both comfortable and healthy.

Margolis’ machine learning is in the area of “clinical support systems,” which are computer programs that can learn to make decisions such as diagnosis, prognosis and treatment of medical conditions. “There are various names for these types of computer programs … such as machine learning, data mining or pattern recognition,” says Margolis, who has collaborated with researchers at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., and at the University of Arizona.

“The work with Moffitt dealt with a newly developed technique that accomplished two difficult tasks: combining the decisions from multiple computer programs intelligently and combining the data from multiple clinical tests intelligently,” Margolis explains. “For example, assume a doctor has several computer programs that try to automatically diagnose lung cancer from a DNA microarray or CT scans. However, each program only works well with certain patients and/or a certain test. This new technique would learn which combination of programs and tests works best for a particular patient.”

The research with Arizona used machine learning to improve methods of evaluating cancer treatment response. “We took the data that is normally used when looking at CT scans, added additional clinical data and then sent it through a machine learning method,” Margolis says. “We showed that machine learning methods could be designed to allow any new type of data to be added, and these methods performed far better than the current ‘gold standard’ method.”

He says they also noticed interesting patterns in “observer variability,” that is, the fact that doctors disagree with each other — and sometimes with themselves. These patterns showed that machine learning methods eventually could be developed to objectively score and train doctors in fields such as radiology.

Margolis says an increase in the use of machines would not affect a patient’s opportunity to receive personalized care. “The goal is for cheaper, better detection methods using computers,” he says. “Nobody would not get the medical test they needed.”

Once he completes his doctorate in systems science, he hopes to work in industrial research. His advisor, Walker Land, predicts success.

“Dan is best described as a unique thinker, one who sees a difficulty as an opportunity rather than a problem,” says Land, research professor of bioengineering. “It’s just the kind of thinking required for successful bioinformatics/biomedical research.”

Paquette, a Binghamton senior, worked last summer with Walker Land, research professor of bioengineering, to analyze gene expression data and predict the recurrence of cancer using a machine learning algorithm called Kernel Partial Least Squared, or KPLS. Similar data mining and artificial intelligence techniques are used by companies such as Amazon and Google to predict searches and rank pages.

“The technology exists and is proven,” Paquette says. “Now it’s a question of: How do we take that and apply it to other fields?”

Apply it he has. Paquette received $5,000 for his application of KPLS research to an InnoCentive project. InnoCentive is a website where industry, businesses and government agencies can tap into a community of problem solvers, and pay a one-time award for rights to the crowd-sourced solution.

The Environmental Defense Fund and Iowa Soybean Growers posted a challenge requesting technology to predict crop yield using nitrogen sensors that would help manage fertilizer use and boost crop productivity. Paquette’s winning idea was to use blimps with on-board sensors that would fly over crops and take nitrogen readings, which would correlate with the vigor of the crop. The information collected would be fed to the farmer’s computer for analysis.

“The guy’s very creative; he can see things that a lot of other students can’t see,” Land says of Paquette. “He thinks about things in a way that most people don’t.”

Paquette plans to pursue a doctorate in machine learning and artificial intelligence. “It’s an exciting field to get into,” he says. “I want to be an expert in it so I can create these systems, maybe make a few bucks and help the world doing it.”

The InnoCentive project inspired Paquette to bring the Web resource to other engineering students. He and some friends started a group devoted to solving InnoCentive challenges. The club facilitates collaborations among students, faculty members and entrepreneurs. “I want to develop a support network for student innovation,” Paquette says. “The University has so many resources, and if you don’t take full advantage of them, what’re you doing? I want to utilize everything I can to my advantage to do something good here.”

Paquette’s summer research inspired a senior design project, too. He’s using the KPLS research to predict the likelihood of lung cancer recurring within five years and to determine whether chemotherapy is necessary.

“Right now, cancer patients are getting chemo when they don’t need it,” Paquette says. “My dad had chemotherapy and it’s terrible. It destroys your quality of life.”

Lead author Gretchen Mahler, assistant professor of bioengineering at Binghamton University, says much of the existing research on the safety of nanoparticles has focused on their direct health effects. But what Mahler, Michael L. Shuler of Cornell University and a team of researchers really wanted to know was what happens when someone receives constant exposure in small doses — the kind you’d get if you were taking a drug or supplement that included nanoparticles in some form.

“We thought that the best way to measure the more subtle effects of this kind of intake was to monitor the reaction of intestinal cells,” Mahler says. “And we did this in two ways: in vitro, through human intestinal-lining cells that we had cultured in the lab; and in vivo, through the intestinal linings of live chickens. Both sets of results pointed to the same thing — that exposure to nanoparticles influences the absorption of nutrients into the bloodstream.”

The uptake of iron, an essential nutrient, was of particular interest because of the way it is absorbed and processed through the intestines. Mahler and the team tested this with polystyrene nanoparticles because of its easily traceable fluorescent properties.

“What we found was that for brief exposures, iron absorption dropped by about 50 percent,” Mahler says. “But when we extended that period of time, absorption actually increased by about 200 percent. It was very clear: Nanoparticles definitely affect iron uptake and transport.”

While acute oral exposure caused disruptions to intestinal iron transport, chronic exposure caused a remodeling of the intestinal villi — the tiny, finger-like projections that are vital to the intestine’s ability to absorb nutrients — making them larger and broader, thus allowing iron to enter the bloodstream much faster.

Humans consume about 100 trillion nanoparticles every day. Although the impact of chronic exposure remains somewhat unknown, the ingestion of dietary particles is thought to promote a range of diseases, including Crohn’s disease. With so many nanomaterials under development and with so much yet to be learned about nanoparticle toxicity and potential human tissue reactivity, Mahler and the team hope that their work, particularly the in vitro model, will provide an effective low-cost screening tool.

They plan to take a look at whether similar disruptions in nutrient absorption could be possible in other inorganic elements, such as calcium, copper and zinc. Also on the research agenda is the reaction of other nutrients such as fat-soluble vitamins A, D, E and K. And chickens and their intestines will definitely be part of this next phase of the study.

“The gastrointestinal tract of a chicken has very similar features to that of a human,” Mahler says. “We can learn a great deal from the way chicken tissue works, which means we can make better predictions about how humans will react.”