OREGON STATE UNIVERSITY

scientific research and advances

Research identifies key genetic link in the biology of aging

CORVALLIS, Ore. – New research at Oregon State University suggests it may be possible to slow age-related disease with new types of treatments.

Scientists have tracked the syndromes associated with aging to their biochemical roots, and identified a breakdown in genetic communication as part of the problem. The findings imply that aging happens for a reason, and that while aspects of it may be inevitable, there could be ways to slow down disease development.

The newest study relate to a protein, Nrf2, that helps regulate gene expression and the body’s reaction to various types of stressors. The research was published in Free Radical Biology and Medicine, in work supported by the National Institutes of Health and the Medical Research Foundation of Oregon.

“We’re very excited about the potential of this area of research,” said Tory Hagen, corresponding author on this study, and the Helen P. Rumbel Professor for Health Aging Research in the Linus Pauling Institute and the OSU Department of Biochemistry and Biophysics in the College of Science.

“At least one important part of what we call aging appears to be a breakdown in genetic communication, in which a regulator of stress resistance declines with age,” Hagen said. “As people age and their metabolic problems increase, the levels of this regulator, Nrf2, should be increasing, but in fact they are declining.”

Nrf2 is both a monitor and a messenger, OSU researchers say. It’s constantly on the lookout for problems with cells that may be caused by the many metabolic insults of life – oxidative stress, toxins, pollutants, and other metabolic dysfunction.

When it finds a problem, Nrf2 essentially goes back to the cellular nucleus and rings the alarm bell, where it can “turn on” up to 200 genes that are responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other actions. In their report, the scientists called it a “longevity-assurance” factor.

Nrf2 is so important that it’s found in many life forms, not just humans, and it’s constantly manufactured by cells throughout the body. About half of it is used up every 20 minutes as it performs its life-protective functions. Metabolic insults routinely increase with age, and if things were working properly, the amount of Nrf2 that goes back into the nucleus should also increase to help deal with those insults.

Instead, the level of nuclear Nrf2 declines, and the OSU scientists say they have discovered why.

“The levels of Nrf2, and the functions associated with it, are routinely about 30-40 percent lower in older laboratory animals,” said Kate Shay, director of the Healthy Aging Core Laboratory at OSU and co-author on this study. “We’ve been able to show for the first time what we believe is the cause.”

The reason for this decline, the scientists said, is increasing levels of a micro-RNA called miRNA-146a.

Micro-RNAs have been one of the most profound scientific discoveries of the past 20 years. They were once thought to be “junk DNA” because researchers could see them but they had no apparent biological role. They are now understood to be anything but junk – they help play a major role in genetic signaling, controlling what genes are “expressed,” or turned on and off to perform their function.

In humans, miRNA-146a plays a significant role. It can turn on the inflammation processes that, in something like a wound, help prevent infection and begin the healing process. But with aging, this study now shows that miRNA-146a expression doesn’t shut down properly, and it can significantly reduce the levels of Nrf2.

This can cause part of the chronic, low-grade inflammation that is associated with the degenerative diseases that now kill most people in the developed world, including heart disease, cancer, diabetes and neurological disease.

“The action of miRNA-146a in older people appears to turn from a good to a bad influence,” Shay said. “It may be causing our detoxification processes to decline just when we need them the most.”

Some of the things found to be healthy for individuals, in diet or lifestyle, may be so because they help to conserve the proper balance between the actions of miRNA-146a and Nrf2, the OSU researchers said. Alternatively, it may be possible to reduce excessive levels of miRNA-146a with compounds that interfere with its function. There may also be other micro-RNAs associated with this process, they said, that need further research.

“Overall, these results provide novel insights for the age-related decline in Nrf2 and identify new targets to maintain Nrf2-dependent detoxification with age,” the researchers wrote in their conclusion.

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Tory Hagen, 541-737-5083

Tooth fillings of the future may incorporate bioactive glass

CORVALLIS, Ore. – A few years from now millions of people around the world might be walking around with an unusual kind of glass in their mouth, and using it every time they eat.

Engineers at Oregon State University have made some promising findings about the ability of “bioactive” glass to help reduce the ability of bacteria to attack composite tooth fillings – and perhaps even provide some of the minerals needed to replace those lost to tooth decay.

Prolonging the life of composite tooth fillings could be an important step forward for dental treatment, the researchers say, since more than 122 million composite tooth restorations are made in the United States every year. An average person uses their teeth for more than 600,000 “chews” a year, and some studies suggest the average lifetime of a posterior dental composite is only six years.

The new research was just published in the journal Dental Materials, in work supported by the National Institutes of Health.

“Bioactive glass, which is a type of crushed glass that is able to interact with the body, has been used in some types of bone healing for decades,” said Jamie Kruzic, a professor and expert in advanced structural and biomaterials in the OSU College of Engineering.

“This type of glass is only beginning to see use in dentistry, and our research shows it may be very promising for tooth fillings,” he said. “The bacteria in the mouth that help cause cavities don’t seem to like this type of glass and are less likely to colonize on fillings that incorporate it. This could have a significant impact on the future of dentistry.”

Bioactive glass is made with compounds such as silicon oxide, calcium oxide and phosphorus oxide, and looks like powdered glass. It’s called “bioactive” because the body notices it is there and can react to it, as opposed to other biomedical products that are inert. Bioactive glass is very hard and stiff, and it can replace some of the inert glass fillers that are currently mixed with polymers to make modern composite tooth fillings.

“Almost all fillings will eventually fail,” Kruzic said. “New tooth decay often begins at the interface of a filling and the tooth, and is called secondary tooth decay. The tooth is literally being eroded and demineralized at that interface.”

Bioactive glass may help prolong the life of fillings, researchers say, because the new study showed that the depth of bacterial penetration into the interface with bioactive glass-containing fillings was significantly smaller than for composites lacking the glass.

Fillings made with bioactive glass should slow secondary tooth decay, and also provide some minerals that could help replace those being lost, researchers say. The combination of these two forces should result in a tooth filling that works just as well, but lasts longer.

Recently extracted human molars were used in this research to produce simulated tooth restoration samples for laboratory experiments. OSU has developed a laboratory that’s one of the first in the world to test simulated tooth fillings in conditions that mimic the mouth.

If this laboratory result is confirmed by clinical research, it should be very easy to incorporate bioactive glass into existing formulations for composite tooth fillings, Kruzic said.

The antimicrobial effect of bioactive glass is attributed, in part, to the release of ions such as those from calcium and phosphate that have a toxic effect on oral bacteria and tend to neutralize the local acidic environment.

“My collaborators and I have already shown in previous studies that composites containing up to 15 percent bioactive glass, by weight, can have mechanical properties comparable, or superior to commercial composites now being used,” Kruzic said.

This work was done in collaboration with researchers from the School of Dentistry at the Oregon Health & Science University and the College of Dental Medicine at Midwestern University.

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Jamie Kruzic, 541-737-7027

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Harbor seal deaths show presence of bacterial infection

CORVALLIS, Ore. – A study by microbiologists at Oregon State University has concluded that an unsuspected bacterial infection, rather than a viral disease, was associated with the stranding and death of seven harbor seals on the California coast in 2009.

The research, made with a powerful investigative method called “meta-transcriptomics,” found a high incidence of infection in the seals with the bacterial pathogen Burkholderia, and provides the first report in the Americas of this bacteria in a wild harbor seal.

The bacteria probably did not directly cause the death of the seals, researchers say, but this provides  further evidence of the increase in emerging marine pathogens, and the need for improved monitoring and study of zoonotic diseases that could affect both human and wildlife populations.

In light of these findings, OSU researchers also remind the public that they should not touch stranded or dead marine mammals.

The research was recently published in PLOS ONE, in work supported by the Oregon Sea Grant program and the National Science Foundation.

“We now have improved tools to better identify new diseases as they emerge from natural reservoirs, and can record and track these events,” said Rebecca Vega-Thurber, an assistant professor of microbiology in the OSU College of Science. “It’s becoming clear there are more pathogens than we knew of in the past, and that some of them can move into human populations.

“This is why it’s increasingly important that we accurately pinpoint the cause of these diseases, and understand the full range of causes that may factor into these deaths.”

Cases such as this, the researchers said, point out that it’s not always a single pathogen that causes death, but a combination of pathogens, changing environmental influences, weakened hosts and other forces. In this seal-stranding event, the scientists also found evidence of Coxiella burnettii, another bacterial pathogen, at high levels in one animal.

Advances in this type of monitoring are being made with the comparatively new field of meta-transcriptomics, which has been referred to as a way to eavesdrop on the viral and microbial world, to catalogue and compare sequences from suspected pathogens. It’s just now being applied to marine systems, which are often reservoirs for pathogens that can emerge into terrestrial populations.

This phenomenon seems to be picking up speed, the researchers noted in their study.

About 61 percent of emerging human diseases arise from zoonotic pathogens, and about 70 percent of these originate from wildlife. The recent Ebola outbreak in Africa was one example; the bacterial pathogen that causes tuberculosis was introduced to the Americas from pinnipeds; and influenza has been shown to be transmitted from seals to humans.  In recent years, viral disease has been implicated in the deaths of tens of thousands of harbor seals.

Almost half of marine mammals die from unknown causes, the researchers said, but the use of new high-speed, analytic tools could offer ways to change that. The techniques don’t require prior information about the viruses and bacterial infections that may be affecting wildlife.

In the case of the stranded harbor seals in this study, it was initially suspected that viruses were the cause. This study largely ruled that out, but identified bacterial infection in the animals’ brains. The final cause of death is still unknown and research on that issue is continuing.

“These analytic tools should be increasingly useful in the future, and show us just what genes the pathogens may be using during an infection,” said Stephanie Rosales, a doctoral student in the OSU College of Science, and lead author on this study.  “A lot of new environmental changes and stresses are taking place that may lead to new emerging diseases, and we should be tracking them as they evolve.”

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Rebecca Vega-Thurber, 541-737-1851

OSU/NOAA study: Warm-water years are tough on juvenile salmon

NEWPORT, Ore. – A new analysis of juvenile Chinook salmon in the Pacific Ocean documents a dramatic difference in their foraging habits and overall health between years of warm water and those when the water is colder.

The study found that when the water is warmer than average – by only two degrees Celsius – young salmon consume 30 percent more food than during cold-water regimes. Yet they are smaller and skinnier during those warm-water years, likely because they have to work harder to secure food and the prey they consume has less caloric energy.

Results of the research, conducted by researchers from Oregon State University and the National Oceanic and Atmospheric Administration, are being published this week in the journal PLOS One.

“When young salmon come out to sea and the water is warm, they need more food to keep their metabolic rate up, yet there is less available food and they have to work harder,” said Elizabeth Daly, an Oregon State senior faculty research assistant with the Cooperative Institute for Marine Resources Studies, a joint program of OSU and NOAA.

“Our long-term data set contradicts the long-held assumption that salmon eat less during warm-water regimes,” Daly added. “They actually eat more. But they still don’t fare as well. When the water is warm, salmon are smaller and thinner.”

Daly teamed with Richard Brodeur, a NOAA Northwest Fisheries Science Center researcher, to examine 19 years of juvenile salmon surveys, from 1981-85 and 1998-2011. The rich, long-term data set revealed the trophic habits, size and condition of yearling Chinook salmon caught soon after they migrated to the ocean. The researchers found that during both warm- and cold-water regimes, the diet of the salmon is primarily fish, but when the water is cold, they also consume more lipid-rich krill and Pacific sand lance. When the water is warmer, the salmon’s diet had more juvenile rockfish and crab larvae.

Previous research led by Bill Peterson, a NOAA fisheries biologist and courtesy professor in OSU’s College of Earth, Ocean, and Atmospheric Sciences (CEOAS), found that the makeup of copepods during cold-water years differs greatly than during warm-water years. In cold years, these small crustaceans drift down from the north and are lipid-rich, with much higher nutrient levels than copepods from the south.

And though salmon may not directly consume these copepods, they are eating the fish that do consume them, noted Brodeur, also a courtesy faculty member in CEOAS.

“The warm years typically have less upwelling that brings the cold, nutrient-rich water to the surface,” Brodeur said. “Or in the case of 2005, the upwelling was so late that many of the salmon died because there was no food when they entered the ocean.”

“Salmon populations may be able to handle one year of warm temperatures and sparse food,” Brodeur added. “But two or three years in a row could be disastrous – especially for wild fish populations. They may have to travel much farther north to find any food.”

Hatchery-raised salmon that are released in similar numbers in warm- or cold-water years may fare slightly better during bad ocean conditions, the researchers noted, because they tend to be larger when they enter the marine environment.

Daly and Brodeur, who work out of OSU’s Hatfield Marine Science Center in Newport, Oregon, said that the 19 survey years they analyzed included 10 warm-water years and nine cold-water years. In some cases, the warm water was a result of an El Niño, while in other years it was a lack of upwelling.

During the last two years, an unusually large, warm body of water has settled into the ocean off the Pacific Northwest that scientists have dubbed “The Blob,” which is forecast to be followed this winter by a fairly strong El Niño event. Though recent spring Chinook salmon runs have been strong due to cooler ocean conditions in 2012-13, the impact of this long stretch of warm water on juvenile fish may bode poorly for future runs.

“So far this year, we’ve seen a lot of juvenile salmon with empty stomachs,” Daly said. “The pressure to find food is going to be great. Of those fish that did have food in their stomachs, there was an unusual amount of juvenile rockfish and no signs of Pacific sand lance or krill.

“Not only does this warm water make it more difficult for the salmon to find food, it increases the risk of their own predation as they spend more time eating and less time avoiding predators,” she added.

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Elizabeth Daly, 541-867-0404; elizabeth.daly@oregonstate.edu;

Ric Brodeur, 541-867-0335, Richard.Brodeur@noaa.gov

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Oregon Sea Grant announces 2016-18 research grant recipients

CORVALLIS, Ore. – Oregon Sea Grant, a marine research, outreach, education and communication program based at Oregon State University, is awarding $1.7 million in competitive, federally funded research grants for 2016-18.

The grants will go to eight principal investigators at OSU, Oregon Health & Science University, and the University of Oregon for research into marine-related issues.

"Oregon Sea Grant is committed to supporting the science needed to address challenges facing our coastal communities and ecosystems,” said Shelby Walker, director of Oregon Sea Grant. “These projects reflect a broad array of issues important to the future of coastal Oregonians, communities and our environment."

The projects and their principal investigators are listed below (click on the links for additional information):

  • “Indexing the vulnerability and adaptive capacity of marine shellfish to combined stressors of ocean acidification and hypoxia,” Francis Chan, OSU Department of Integrative Biology. (Co-PIs are Eli Meyer and Kristin Milligan, OSU; and Steven Rumrill, Oregon Department of Fish and Wildlife) More information.
  • “Does ocean productivity contribute to dune ecosystem function? Connecting wrack subsidies to Oregon dune coastal protection and conservation services,” Sally Hacker, OSU Department of Integrative Biology. (Co-PIs are Peter Ruggiero and Francis Chan, OSU) More information.
  • “Distribution and degradation of the anti-diabetic drug, Metformin, and its breakdown product, guanylurea, in the Columbia River basin,” Tawnya Peterson, OHSU Institute of Environmental Health. (Co-PI is Joseph Needoba, OHSU). More information.
  • “Utilizing uranium-to-calcium ratios to determine best management practices for shell planting and oyster culture to mitigate ocean acidification impacts,” Alyssa Shiel, OSU College of Earth, Ocean, and Atmospheric Sciences. (Co-PIs Adam Kent and George Waldbusser, OSU). More information.
  • “Improving coastal ocean forecasting and visualization through collaboration in discovery, learning and practice,” Ted Strub, OSU College of Earth, Ocean, and Atmospheric Sciences. (Co-PIs Flaxen Conway and Alexander Kurapov, OSU). More information.
  • “Predatory impacts of large medusa on ichthyoplankton in the Northern California Current,” Kelly Sutherland, University of Oregon’s Oregon Institute of Marine Biology. (Co-PI Richard Brodeur, NOAA’s Northwest Fisheries Science Center). More information.
  • “Evaluating the vulnerability of Oregon seagrass beds to eutrophication,” Fiona Tomas Nash, OSU Department of Fisheries and Wildlife. (Co-PIs Steven Rumrill and Anthony D’Andrea, ODFW; James Kaldy, U.S. Environmental Protection Agency; Bree Yednock and Joy Tally, South Slough National Estuarine Research Reserve; and Renee O’Neill, OSU). More information.
  • “Competing effects of relative sea-level rise and fluvial inputs on blue carbon sequestration in Oregon salt marshes,” Robert Wheatcroft, OSU College of Earth, Ocean, and Atmospheric Sciences. (Co-PIs Laura Brophy and Michael Ewald, Institute for Applied Ecology; Erin Peck, OSU). More information.

As part of the National Oceanic and Atmospheric Administration’s nationwide Sea Grant College Program, Oregon Sea Grant receives a share of congressionally appropriated research dollars every two years to award via a competitive process to university-based scientists studying ocean and coastal issues important to the region and the nation.

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Shelby Walker, 541-737-6200, Shelby.walker@oregonstate.edu

72 scientists ink letter to U.S. presidential candidates urging leadership on clean energy

CORVALLIS, Ore. – A group of 72 leading climate change scientists have written a letter to major United States presidential candidates urging strong American leadership on clean energy – and calling for a “vibrant economy free from carbon pollution by mid-century.”

The effort began as a letter from nine scientists from Harvard University, Stanford University, University of California at Berkeley, Tufts and elsewhere – part of the Union of Concerned Scientists. Other scientists, including Philip Mote of Oregon State University, recently joined the initiative.

Mote, who directs the Oregon Climate Change Research Institute at Oregon State, and also provides leadership on two joint federal climate change centers at the university, said focusing on clean, renewable sources of energy is not a choice between a strong economy and a healthy environment.

“These are not mutually exclusive,” said Mote, a professor in OSU’s College of Earth, Ocean, and Atmospheric Sciences. “Many of the largest and most influential companies in the world are using energy from renewable sources, including Apple, Google and others. It’s not just a good environmental strategy – they see it as a good business strategy.”

“Oregon’s emission of greenhouse gases peaked in 1999 and has been declining, showing that we can grow the economy and reduce emissions,” Mote added.

In their letter, the climate scientists point to the gradual shift away from non-sustainable fossil fuels to solar and wind power – in part because of rapidly advancing technology. The next U.S. president “will be uniquely positioned to ensure that our nation sustains and accelerates this transition,” they wrote. “The dangers of inaction are also increasingly apparent and lend great urgency to this appeal.”

The letter is being released this week as policy-makers and others convene in Paris for the annual international climate summit.  Limiting carbon emissions from fossil fuels is critical in slowing the rate of warming the Earth is experiencing, the scientists note, and the effects are being seen world-wide – from rapidly warming and acidifying oceans to melting glaciers.

Yet much of the public – and many political leaders – has been slow to accept what many scientists say is overwhelming evidence that our planet is in peril, Mote said.

“This week, as some of Oregon’s rivers are rising, we are reminded that a warming climate accentuates existing risks like flooding,” Mote said.  “Additional risks for the region include increased wildfires and coastal inundation. Limiting emissions will reduce the size of future changes."

The scientists call for the next president to pursue key goals, including:

  • Following through on the U.S. commitment to reduce carbon emissions by 26 to 28 percent below 2005 levels by the year 2025;
  • Phasing out fossil energy subsidies and putting a price on carbon to “ensure a level playing field” for renewable energy, nuclear power and other low- or zero-carbon technologies;
  • Modernizing antiquated energy transmission, distribution and transportation systems;
  • Increasing investment in clean energy research.

Mote was a lead author on the 2007 Intergovernmental Panel on Climate Change report, which led to a Nobel Prize, and a lead author for the fifth IPCC report in 2013 in a chapter focusing on the cryosphere.

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Phil Mote, 541-737-5692, pmote@coas.oregonstate.edu

Report: Willamette Valley water future mostly bright, though gaps may need to be addressed

CORVALLIS, Ore. – During the next 85 years, temperatures in Oregon’s Willamette River basin are expected to rise significantly, mountain snowpack levels will shrink dramatically, and the population of the region and urban water use may double – but there should be enough water to meet human needs, a new report concludes.

Fish may not be so lucky. Although ample water may be available throughout most of the year, the Willamette Valley and its tributaries likely will become sufficiently warm as to threaten cold-water fish species, including salmon and steelhead, the scientists say.

These are among the key findings of the Willamette Water 2100 Project, a five-year, $4.3 million study funded by the National Science Foundation and led by Oregon State University, in partnership with researchers from the University of Oregon, Portland State University and University of California at Santa Barbara.

“The Willamette River basin today is characterized by abundant annual water and sometime seasonal shortages,” said Anne Nolin, an OSU professor of environmental sciences and principal investigator on the study. “That should continue into 2100, despite much warmer temperatures, more people and a substantial loss of snowpack.

“The reason for optimism is the region’s 11 storage reservoirs coordinated by the Army Corps of Engineers that act as a valve for seasonal differences and preserve water for times of need,” Nolin added. “Without them, the picture would look quite a bit different.”

Analysis of global circulation models suggest that the Willamette River basin will warm between two and 13 degrees (Fahrenheit) by the year 2100, thus scientists used three separate scenarios to look at potential impacts based on low, medium and high rates of temperature increase. These temperature increases will result in a dramatic decline in snowpack – from 63 to 95 percent lower than average – changing seasonal water flow patterns.

Scientists also explored results from a range of population, economic and policy scenarios that allowed them to ask “what if?” questions for different human changes and interactions with climate changes. Much of the climate modeling for the project was developed through a regional integrated sciences and assessments (RISA) program at Oregon State, which is funded by NOAA and led by OSU Professor Philip Mote.

There is little doubt that temperatures will increase, the report notes, but there is less certainty about the impact of a changing climate on precipitation. Winters may actually be slightly wetter, though more of the precipitation will fall as rain instead of snow. Summers should be drier, necessitating more reliance on water held behind the region’s 11 storage reservoirs.

“Although there are a number of government entities – federal and state – involved in regulating water use from those reservoirs, there appears to be enough flexibility in the system to adequately adapt for changing conditions in the future,” said Nolin, a professor in OSU’s College of Earth, Ocean, and Atmospheric Sciences.

The report notes that warmer temperatures, less snowpack and drier summers will greatly increase the danger of wildfire in the mountains feeding the Willamette River basin – by about 200 to 900 percent. Their simulations show that fire will open up lands to new forest types and reduce the availability of forestland for timber harvest.

Increasing urban use of water from a population that could double will involve costly expansions in infrastructure. As the population grows, more agricultural land near urban areas will be developed for housing and other needs, according to Samuel Chan, a watershed health specialist with Oregon Sea Grant and the broader impacts outreach lead for the Willamette Water 2100 Project.

However, the report shows that in some cases where urban areas are expanding into what are now irrigated farmlands, these locations may see a net decline in water use.

“The report notes the difference between water ‘diversions’ and water ‘consumptive use,’” Chan noted. “As the population grows, the need for water will increase, but much of it will be used, and then treated in wastewater plants and returned to the system. Other uses, like forests and agriculture, consume the water through evaporation and transpiration to the atmosphere.”

“The downside, though, is that treated water that is returned to the river is often warmer, increasing the impact on cold-water fish species,” he added.

The main drivers for changing water needs, the report concludes, are climate change, and growth in population and income.

“The dams built above the Willamette Valley were engineered for reducing the risk of floods, but they also do a valuable job in storing water for use during summer,” Nolin said. “They can store large amounts of water in the summer, when they are not kept empty for flood prevention and there is existing flexibility in water allocation policies that could help western Oregon adapt to a climate that may be quite different in the future.”

“Unlike many parts of the country, those of us who live in the Willamette Valley are lucky because we have abundant water for human use, and we have institutional capacity to help mitigate water scarcity,” she added. “However, the biggest negative impacts are likely to be for native cold-water fish and we will likely be facing a significant challenge in managing stream temperature for fish.”

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Anne Nolin, 541-737-8051, nolina@geo.oregonstate.edu;

Sam Chan, (cell: 503-679-4828), Samuel.chan@oregonstate.edu

Photonic “sintering” may create new solar, electronics manufacturing technologies

CORVALLIS, Ore. – Engineers at Oregon State University have made a fundamental breakthrough in understanding the physics of photonic “sintering,” which could lead to many new advances in solar cells, flexible electronics, various types of sensors and other high-tech products printed onto something as simple as a sheet of paper or plastic.

Sintering is the fusing of nanoparticles to form a solid, functional thin-film that can be used for many purposes, and the process could have considerable value for new technologies.

Photonic sintering has the possible advantage of higher speed and lower cost, compared to other technologies for nanoparticle sintering.

In the new research, OSU experts discovered that previous approaches to understand and control photonic sintering had been based on a flawed view of the basic physics involved, which had led to a gross overestimation of product quality and process efficiency.

Based on the new perspective of this process, which has been outlined in Nature Scientific Reports, researchers now believe they can create high quality products at much lower temperatures, at least twice as fast and with 10 times more energy efficiency.

Removing constraints on production temperatures, speed and cost, the researchers say, should allow the creation of many new high-tech products printed onto substrates as cheap as paper or plastic wrap.

“Photonic sintering is one way to deposit nanoparticles in a controlled way and then join them together, and it’s been of significant interest,” said Rajiv Malhotra, an assistant professor of mechanical engineering in the OSU College of Engineering. “Until now, however, we didn’t really understand the underlying physics of what was going on. It was thought, for instance, that temperature change and the degree of fusion weren’t related – but in fact that matters a lot.”

With the concepts outlined in the new study, the door is open to precise control of temperature with smaller nanoparticle sizes. This allows increased speed of the process and high quality production at temperatures at least two times lower than before. An inherent “self-damping” effect was identified that has a major impact on obtaining the desired quality of the finished film.

“Lower temperature is a real key,” Malhotra said. “To lower costs, we want to print these nanotech products on things like paper and plastic, which would burn or melt at higher temperatures. We now know that is possible, and how to do it. We should be able to create production processes that are both fast and cheap, without a loss of quality.”

Products that could evolve from the research, Malhotra said, include solar cells, gas sensors, radiofrequency identification tags, and a wide range of flexible electronics. Wearable biomedical sensors could emerge, along with new sensing devices for environmental applications.

In this technology, light from a xenon lamp can be broadcast over comparatively large areas to fuse nanoparticles into functional thin films, much faster than with conventional thermal methods. It should be possible to scale up the process to large manufacturing levels for industrial use.

This advance was made possible by a four-year, $1.5 million National Science Foundation Scalable Nanomanufacturing Grant, which focuses on transcending the scientific barriers to industry-level production of nanomaterials. Collaborators at OSU include Chih-hung Chang, Alan Wang and Greg Herman.

OSU researchers will work with two manufacturers in private industry to create a proof-of-concept facility in the laboratory, as the next step in bringing this technology toward commercial production.

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Discovery could open door to frozen preservation of tissues, whole organs

CORVALLIS, Ore. – Researchers in the College of Engineering at Oregon State University have discovered a new approach to “vitrification,” or ice-free cryopreservation, that could ultimately allow a much wider use of extreme cold to preserve tissues and even organs for later use.

The findings were announced today in PLOS ONE, in work supported by the National Science Foundation.

“This could be an important step toward the preservation of more complex tissues and structures,” said Adam Higgins, an associate professor in the OSU School of Chemical, Biological and Environmental Engineering, and expert on medical bioprocessing.

Cryopreservation has already found widespread use in simpler applications such as preserving semen, blood, embryos, plant seeds and some other biological applications. But it is often constrained by the crystallization that occurs when water freezes, which can damage or destroy tissues and cells, Higgins said. This is similar to what happens to some food products when they are stored in a freezer, and lose much of their texture when thawed.

To address this, researchers have used various types of cryoprotectants that help reduce cell damage during the freezing process – among them is ethylene glycol, literally the same compound often used in automobile radiators to prevent freezing.

A problem, Higgins said, is that many of these cryoprotectants are toxic, and can damage or kill the very cells they are trying to protect from the forces of extreme cold.

In the new OSU research, the engineers developed a mathematical model to simulate the freezing process in the presence of cryoprotectants, and identified a way to minimize damage. They found that if cells are initially exposed to a low concentration of cryoprotectant and time is allowed for the cells to swell, then the sample can be vitrified after rapidly adding a high concentration of cryoprotectants. The end result is much less overall toxicity, Higgins said.

The research showed that healthy cell survival following vitrification rose from about 10 percent with a conventional approach to more than 80 percent with the new optimized procedure.

“The biggest single problem and limiting factor in vitrification is cryoprotectant toxicity, and this helps to address that,” Higgins said. “The model should also help us identify less toxic cryoprotectants, and ultimately open the door to vitrification of more complex tissues and perhaps complete organs.”

If that were possible, many more applications of vitrification could be feasible, especially as future progress is made in the rapidly advancing field of tissue regeneration, in which stem cells can be used to grow new tissues or even organs.

Tissues could be made in small amounts and then stored until needed for transplantation. Organs being used for transplants could be routinely preserved until a precise immunological match was found for their use. Conceptually, a person could even grow a spare heart or liver from their own stem cells and preserve it through vitrification in case it was ever needed, Higgins said.

Important applications might also be found in new drug development.

Drug testing is now carried out with traditional cell culture systems or animal models, which in many cases don’t accurately predict the effect of the drug in humans. To address this, researchers are developing “organs-on-a-chip,” or microfluidic chambers that contain human cells cultured under conditions that mimic native tissues or organs.

These new “organ-on-a-chip” systems may be able to more accurately predict drug responses in humans, but to deploy them, cells must be preserved in long-term storage. The new research could help address this by making it possible to store the systems in a vitrified state.

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Adam Higgins, 541-737-6245

Barriers to health care increase disease, death risk for rural elderly

CORVALLIS, Ore. – A new study of adults ages 85 or older has found that rural residents have significantly higher levels of chronic disease, take more medications, and die several years earlier than their urban counterparts.

The findings were just published in The Journal of Rural Health by researchers from Oregon State University and the Oregon Health & Science University.

The research confirms some of the special challenges facing older populations in rural or remote areas, who often have less access to physicians, long distances to travel for care, sometimes a lower socioeconomic and educational level, and other issues. It also reflects health problems that might have been reduced if they were treated earlier or more aggressively, researchers say.

Data from several different study groups found that rural residents measured significantly higher on the Modified Cumulative Illness Rating Scale, with about an 18 percent higher disease burden.

“It’s been known for some time that health care is harder to access in rural areas, and this helps us better understand the extent of the problem,” said Leah Goeres, a postdoctoral scholar who led the research at the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Many physicians do the best they can in rural areas given the challenges they face,” Goeres said. “But there are fewer physicians, fewer specialists, a higher caseload. Doctors have less support staff and patients have less public transportation. A patient sometimes might need to wait months to see a doctor, and have to drive significant distances. Adverse effects can increase from taking multiple medications.

“These are real barriers to choice and access, and they affect the quality of care that’s available.”

Also worth noting, Goeres said, is that especially in very old populations, illness can lead to more illness and quickly spiral out of control. A patient in an urban setting might receive prompt treatment for a mild ulcer, whereas the same person in a rural setting might have to wait while the condition worsens and may even lead to cancer.

“It’s of particular concern that rural older adults start with more disease burden, which significantly increased over the next five years, but the average number of medications they used decreased over the same time period,” said David Lee, an assistant professor in the OSU College of Pharmacy who oversaw the research.

“This may be due to difficulty accessing health care, leading to more disease burden over time, yet less use of medications,” Lee said. “The opposite trends are seen in urban older adults.”

This research was done in Oregon with three cohorts of older adults, one rural and two urban, and 296 people altogether. It was supported by the Oregon Alzheimer’s Disease Tax Checkoff Fund and the National Institutes of Health.

The findings of the new study include:

  • The rural population of Oregon contains a greater proportion of older adults than the urban population.
  • The use of many medications can be especially risky for people in their 80s and 90s, leading to a concern called “polypharmacy” when a person takes five or more medications.
  • Rural participants were found to use an average of 5.5 medications, compared to 3.7 for urban participants.
  • At baseline measurements, valuable medications to aid bone mineralization were often used less in rural populations, but pain-killing opioids were used more often.
  • Medication use for high blood pressure went up significantly over time for rural populations, but not urban ones, in which their use had already been higher.  
  • The rate of disease accumulation was significant in the rural cohort, and negligible in their urban counterparts.
  • The median survival time of the rural cohort was 3.5 years, compared to 7.1 years for the urban older adults.
  • Risk factors of chronic diseases were low education, poor socioeconomic status, a history of chronic disease, being female, and older age. These factors are associated with a typical rural population.
  • Living with someone, and/or having a large social network are protective factors against chronic disease, and may be more common in an urban or suburban population.
  • Both urban and rural residents used a large number of over-the-counter agents, including vitamins, minerals and herbal supplements.

Increased access to health care, health education, increased supervision from clinicians, and better management of both prescription and over-the-counter medications could all be of value in helping rural residents to live longer and healthier livers, the researchers said in their conclusion.

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David Lee, 503-494-2258