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Rensselaer Polytechnic Institute (RPI)

Research 2017

In laboratories, field studies, and simulations, fresh answers can only be seen by those who know how to take a step back, notice what does not fit, test outlier hypotheses, and shift contexts.

Those who explore, discover, and invent often observe in three ways.

First, they are able to look without expectation. It is only with an unrestricted, unaffected view that faint and nuanced changes make themselves known. Some will stand out as pivotal and important. And there always will be a few that only reveal themselves as they come together.

Second, from the exciting vision of what is, where things are going, and what might be next, they identify the big idea, the killer app, or the formula that matters. Like a jeweler discerning the exact place to strike a diamond, they cleave reality in a way that exposes the most important possibilities.

Third, they visualize impacts beyond themselves and their focus areas, such as a chemist who sees not only the beauty of a new synthesis, but recognizes the contributions to medicine, agriculture, and industry that its discovery suggests.

For either of the first two ways of seeing, tools, such as simulation—a major focus at Rensselaer—can reveal the world in new ways that facilitate and augment unrestricted, novel views and make intuitive leaps to elegant concepts easier.

For the third way of seeing, the essential path must be collaboration with people who are experts in different disciplines and who see the world from alternative perspectives. It is part of why Rensselaer has worked to engender conversations and teaming among diverse people across many fields of intellectual endeavor. It is why we continually reach beyond our campuses, too, inviting and engaging with those who grapple with global challenges and the complexities of science, technology, society, and nature.

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Big Data

Tracking the Circadian Clock

Biology dictates that DNA creates proteins that create—among other things—metabolites, the outputs of metabolism. In organisms from fungi to humans, the relationship between these players is heavily influenced by our internal circadian clock, and responds to environmental influences (such as a prolonged day) with implications for industry as well as human health.

“Many disorders associated with disrupting our circadian clocks have links to inflammation, which is an immune system response,” said Jennifer Hurley, assistant professor of biological sciences.

“I think that by disrupting our clocks, we may be altering our metabolic output and chronically inflaming our bodies.”

But the system, which is enormously complex, is poorly understood.

To better understand this system, researchers at Rensselaer, Dartmouth, and the Pacific Northwest National Laboratory are collaborating on a project that uses data—tracking levels of RNA and protein in a cell as they fluctuate with the day/night cycle—to create a computer model depicting how the metabolic environment influences cells throughout the circadian day.

“The complexity of this system is phenomenal; the interactions within a single cell could generate millions of data points,” said Hurley, Rensselaer lead on the project, which is supported by a $3.1 million grant from the National Institutes of Health.

“The intricacy is unfathomable by the human mind alone, but computer modeling combined with experimentation can help us to understand this system.”

Hurley, an expert in circadian biology, has built massive data sets that track clock-controlled levels of RNA and protein in Neurospora, a fungus which produces cellulases, proteins useful to the biofuels industry because they break down cellulose in plants.

Researchers will incorporate the data, along with additional information on metabolites and environmental influences that will be gathered in Hurley's lab and at Dartmouth, into a multiscale model capable of reconciling the disparate circadian and metabolic timescales, and predicting how changes in one area propagate through the entire system. With the $658,000 in support that Hurley will receive from this grant, her lab will conduct experiments that validate the model and its predictions.

While the more profound impacts of the research may relate to human biology, the project also may make it possible to boost Neurospora's production of cellulase, a benefit to the biofuels industry.

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Environment

Engineering Efficient Greenhouses

As consumers demand more locally sourced vegetables and the farm-to-table movement continues to build momentum, New York greenhouses are faced with conflicting tasks focused on producing more quality vegetables while reducing overall energy consumption. Now, a newly formed public-private consortium called GLASE—The Greenhouse Lighting and Systems Engineering Consortium, led by researchers at Rensselaer and Cornell University—has been launched to transform the way greenhouses operate in order to reduce electricity use by 70 percent.

The seven-year, $5 million project funded by the New York State Energy Research and Development Authority will advance New York Governor Andrew Cuomo's Clean Energy Standard that aims to have 50 percent of electricity come from renewable energy sources by 2030. Plant physiology expert Tessa Pocock, who serves as a senior research scientist at the Center for Lighting Enabled Systems & Applications (LESA), will lead the work at Rensselaer. Pocock is fascinated by photosynthesis and has conducted research with plants in both academic and industry settings. “GLASE has the potential to create a more sustainable and profitable greenhouse industry. The systems engineering expertise at LESA and the agriculture expertise at Cornell make this an ideal partnership.”

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Environment

Road salt alternatives alter aquatic ecosystems

Rick Relyea lifts the lid of one of the many mesocosms utilized to mimic lake conditions.

Organic additives found in road salt alternatives act as a fertilizer to aquatic ecosystems, promoting the growth of algae and organisms that eat algae, according to research published in the Journal of Applied Ecology. Low levels of magnesium chloride—an alternative type of salt found in the commercial product Clear Lane—boost populations of amphipods, tiny crustaceans that feed on algae and serve as an important food source for fish.

Alternatives and additives to the most common form of road salt, sodium chloride, are marketed as environmentally friendly replacements because they allow highway crews to maintain ice-free roads while applying less salt. But the alternatives and additives may not be without environmental consequences, says Rick Relyea, director of the Jefferson Project at Lake George.

“Additives and alternative salts are presumed to be less environmentally harmful because they let us use less sodium chloride, but what about the potential impact of the additives and salt alternatives themselves?” says Relyea, professor of biological sciences and the David M. Darrin '40 Senior Endowed Chair. “We know almost nothing about the impact of these additives and alternatives on aquatic ecosystems.”

The research is part of the Jefferson Project at Lake George— a collaboration between Rensselaer, IBM Research, and The FUND for Lake George—founded to develop a new model for technologically enabled environmental monitoring and prediction to understand and protect the Lake George ecosystem and freshwater ecosystems around the world.

As part of the Jefferson Project, Relyea's lab has undertaken a series of experiments into the effects of various road salts on diverse aspects of aquatic food webs, with some surprising results. Many of the experiments make use of mesocosms, large outdoor tanks or chutes filled with water and outfitted to mimic lake, wetland, or stream ecosystems.

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Human Health

A blood test for autism

An algorithm based on levels of metabolites found in a blood sample can accurately predict whether a child is on the Autism spectrum of disorder (ASD), based upon a recent study. The algorithm, developed by researchers at Rensselaer, is the first physiological test for autism and opens the door to earlier diagnosis and potential future development of therapeutics.

“Instead of looking at individual metabolites, we investigated patterns of several metabolites and found significant differences between metabolites of children with ASD and those that are neurotypical. These differences allow us to categorize whether an individual is on the Autism spectrum,” said systems biologist Juergen Hahn, professor and head of the Department of Biomedical Engineering. “By measuring 24 metabolites from a blood sample, this algorithm can tell whether or not an individual is on the Autism spectrum, and even to some degree where on the spectrum they land.”

Autism Spectrum Disorder is estimated to affect approximately 1.5 percent of individuals and is characterized as “a developmental disability caused by differences in the brain,” according to the Centers for Disease Control and Prevention. The physiological basis for ASD is not known, and genetic and environmental factors are both believed to play a role. According to the CDC, the total economic costs per year for children with ASD in the United States are estimated between $11.5 billion and $60.9 billion. Research shows that early intervention can improve development, but diagnosis currently depends on clinical observation of behavior, an obstacle to early diagnosis and treatment. Most children are not diagnosed with ASD until after age 4 years. 

“Because we did everything possible to make the model independent of the data, I am very optimistic we will be able to replicate our results with a different cohort,” said Hahn. “This is the first physiological diagnostic and it's highly accurate and specific.”

Researchers have looked at individual metabolites produced by the methionine cycle and the transsulfuration pathways and found possible links with ASD, but the correlation has been inconclusive. Hahn said the more sophisticated techniques he applied revealed patterns that would not have been apparent with earlier efforts.

 

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Building Innovation

The Group Meeting Reimagined

The project will create smart service systems for facilitating long-term technical group meetings using two Rensselaer campus testbeds previously funded by NSF, LESA's "Smart Conference Room" and the Collaborative-Research Augmented Immersive Virtual Environment (CRAIVE) Lab.

Millions of meetings take place every day in the U.S., incurring a tremendous cost in terms of managers' and employees' precious time and salary. To create smart service systems for facilitating long-term technical group meetings, a team of researchers at Rensselaer and industrial partners, led by computer vision expert Richard Radke, is working to design intelligent rooms.

The new project is supported by a  $1 million award from the  National Science Foundation (NSF) Partnership for Innovation: Building Innovation Capacity program.

“Group meetings suffer from serious problems that undermine productivity and collegiality, including overt or unconscious bias, 'groupthink,' fear of speaking, and unfocused discussion,” said Radke, who also serves as deputy director of the NSF Engineering Research Center for Lighting Enabled Systems & Applications (LESA), and professor of electrical, computer, and systems engineering. “Few automatic tools exist for keeping meetings on track, accurately recording who said what, and making group discussions more productive. The goal of this research is to design intelligent rooms that provide facilitation services by identifying meeting participants, understanding their conversations, summarizing discussions, and helping the group efficiently get through an agenda, all without requiring the participants to wear microphones or other sensors.” 

A key aspect of the project is a multi-year study that tracks technical research groups as they hold regular, unscripted meetings in the test beds. According to Radke, the research may have several broader societal impacts. For example, any steps to make group meetings for complex, long-term projects more productive and easier to control would result in immediate economic impact. Additionally, the success of a service system that facilitates long-term group interactions could result in a major opportunity for technology transfer and a highly marketable hardware/software platform for collaboration in domains including business, education, and finance. 

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Biotechnology

Nano-Decoy Lures Human Influenza A Virus to its Doom

portrait of Robert Linhardt
Robert Linhardt

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic acid lures the influenza A virus to its doom. When misted into the lungs, the nanoparticle traps influenza A, holding it until the virus self-destructs.

In a study on immune-compromised mice, the treatment reduced influenza A mortality from 100 percent to 25 percent over 14 days. The novel approach, which is radically different from existing influenza A vaccines, and treatments based on neuraminidase inhibitors, could be extended to a host of viruses that use a similar approach to infecting humans, such as Zika, HIV, and malaria. “Instead of blocking the virus, we mimicked its target—it's a completely novel approach,” said Robert Linhardt, a glycoprotein expert and Rensselaer professor who led the research. “It is effective with influenza and we have reason to believe it will function with many other viruses. This could be a therapeutic in cases where vaccine is not an option, such as exposure to an unanticipated strain, or with immune-compromised patients.”

The project is a collaboration between researchers within the Center for Biotechnology and Interdisciplinary Studies at Rensselaer and several institutions in South Korea including Kyungpook National University.

The new solution targets an aspect of infection that does not change: All hemagglutinin varieties of influenza A must bind to human sialic acid. To trap the virus, the team designed a dendrimer, a spherical nanoparticle with treelike branches emanating from its core. On the outermost branches, they attached molecules, or “ligands,” of sialic acid.

“The major accomplishment was in designing an architecture that is optimized to bind so tightly to the hemagglutinin, the neuraminidase can't squeeze in and free the virus,” said Linhardt. “It's trapped.”

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Human Health

Fighting Chronic Diseases With Cognitive Computing

IBM and Rensselaer have announced the creation of the new Center for Health Empowerment by Analytics, Learning, and Semantics (HEALS). Located on the Rensselaer campus, the HEALS center is a five-year collaborative research effort aimed at researching how the application of advanced cognitive computing capabilities can help people to understand and improve their own health conditions.

“This collaboration between Rensselaer and IBM, which combines our significant research strengths in cognitive computing, could generate insights which will aid clinicians with more effective treatments for individual patients and overall efficiencies in the health-care system,” said President Shirley Ann Jackson. “In this expansion of our long-standing research partnership with IBM, I am pleased that HEALS will advance preventive health care.”

“Cognitive computing is poised to transform every profession, industry, and economy, and IBM is committed to helping to solve the world's biggest health challenges,” said John Kelly III '78, senior vice president, cognitive solutions and research at IBM. “We are excited to collaborate with Rensselaer on the development of the HEALS research center to advance precision medicine with the help of Watson technologies and to help improve the quality of care clinicians can deliver to individuals.”

The new center's vision is to advance the understanding of chronic disease prevention through data-driven discovery and analysis of factors that can help predict the propensity to develop chronic conditions and provide personalized health recommendations and lifestyle guidance for clinicians to deliver to their patients.

Specifically, the center plans to develop cognitive tools for health empowerment that use analytics, knowledge-driven learning, and semantics-based interrogation to address data-to-knowledge gaps to enable clinicians and patients to help manage and prevent chronic diseases and conditions.

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Human Health

Diet and Back Pain: What's the Link?

portrait of Robert Linhardt
Research indicates the accumulation of AGEs causes structural deterioration, increases inflammation that could lead to disc degeneration, and contributes to a host of degenerative diseases such as diabetes, atherosclerosis, and Alzheimer's. The project is supported by a $3.3 million grant from the National Institutes of Health.

Can a diet high in processed fat and sugar and Type 2 diabetes cause degeneration of intervertebral discs in the spine? If so, what is happening, and can it be prevented? As part of an ongoing collaboration between Rensselaer and the Icahn School of Medicine at Mount Sinai—a partnership that draws upon the expertise of both schools to address significant health problems—researchers hope to answer those questions by investigating the link between diet, obesity-linked Type 2 diabetes, and intervertebral disc degeneration. 

Researchers on the project suspect the diet associated with Type 2 diabetes—one high in processed fats and sugars—causes inflammation and modification of disc tissue, triggering a chain of responses, which leads to degeneration. To test this hypothesis, the researchers have set three goals: to establish whether mice fed a diet associated with Type 2 diabetes will develop intervertebral disc degeneration, isolate the effect of diet causing changes in the tissue, and evaluate how the diet modifies proteins within the disc.

Deepak Vashishth, a professor of biomedical engineering and the Rensselaer lead on the project, said the partnership makes it possible to tackle a project of this complexity.

“We're trying to establish the mechanism whereby this diet, and Type 2 diabetes, leads to disc degeneration, and that's not an easy thing to do because, within the body, various processes are linked and feedback loops are difficult to unravel,” said Vashishth, who is also the director of the Center for Biotechnology and Interdisciplinary Studies. “To investigate this question, you need the mix of experts from different disciplines with different skill sets that the partnership allows.”

At the core of the research project are the effects of advanced glycation endproducts (AGE)—proteins or lipids that have become coated in sugars, which damage their function. Research suggests that a diet high in heat-processed foods, including fried foods, plays a role in AGE formation.

At Rensselaer, researchers will analyze various mouse and human tissue samples, helping to determine how healthy disc tissue in humans and mice differs from the tissue of patients and mice that have developed disc degeneration, as well as mice that have been treated with a drug intended to block the effects of a diet high in AGEs on the spine.

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