OREGON STATE UNIVERSITY

scientific research and advances

“Molecular movie” technology may enable big gains in bioimaging, health research

CORVALLIS, Ore. – Researchers today announced the creation of an imaging technology more powerful than anything that has existed before, and is fast enough to observe life processes as they actually happen at the molecular level.

Chemical and biological actions can now be measured as they are occurring or, in old-fashioned movie parlance, one frame at a time. This will allow creation of improved biosensors to study everything from nerve impulses to cancer metastasis as it occurs.

The measurements, created by the use of short pulse lasers and bioluminescent proteins, are made in femtoseconds, which is one-millionth of one-billionth of a second. A femtosecond, compared to one second, is about the same as one second compared to 32 million years.

That’s a pretty fast shutter speed, and it should change the way biological research and physical chemistry are being done, scientists say.

Findings on the new technology were published today in Proceedings of the National Academy of Sciences, by researchers from Oregon State University and the University of Alberta.

“With this technology we’re going to be able to slow down the observation of living processes and understand the exact sequences of biochemical reactions,” said Chong Fang, an assistant professor of chemistry in the OSU College of Science, and lead author on the research.

“We believe this is the first time ever that you can really see chemistry in action inside a biosensor,” he said. “This is a much more powerful tool to study, understand and tune biological processes.”

The system uses advanced pulse laser technology that is fairly new and builds upon the use of “green fluorescent proteins” that are popular in bioimaging and biomedicine. These remarkable proteins glow when light is shined upon them. Their discovery in 1962, and the applications that followed, were the basis for a Nobel Prize in 2008.

Existing biosensor systems, however, are created largely by random chance or trial and error. By comparison, the speed of the new approach will allow scientists to “see” what is happening at the molecular level and create whatever kind of sensor they want by rational design. This will improve the study of everything from cell metabolism to nerve impulses, how a flu virus infects a person, or how a malignant tumor spreads.

“For decades, to create the sensors we have now, people have been largely shooting in the dark,” Fang said. “This is a fundamental breakthrough in how to create biosensors for medical research from the bottom up. It’s like daylight has finally come.”

The technology, for instance, can follow the proton transfer associated with the movement of calcium ions – one of the most basic aspects of almost all living systems, and also one of the fastest. This movement of protons is integral to everything from respiration to cell metabolism and even plant photosynthesis.  Scientists will now be able to identify what is going on, one step at a time, and then use that knowledge to create customized biosensors for improved imaging of life processes.

“If you think of this in photographic terms,” Fang said, “we now have a camera fast enough to capture the molecular dance of life. We’re making molecular movies. And with this, we’re going to be able to create sensors that answer some important, new questions in biophysics, biochemistry, materials science and biomedical problems.”

The research was supported by OSU, the University of Alberta, the Natural Sciences and Engineering Research Council of Canada, and the Canadian Institutes of Health Research.

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Chong Fang, 541-737-6704

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Molecular movies

NSF awards $200,000 to develop technology to treat sepsis, a global killer

CORVALLIS, Ore. – The National Science Foundation has just awarded $200,000 to engineers at Oregon State University who have developed a new technology that they believe could revolutionize the treatment and prevention of sepsis.

Sepsis is a “hidden killer” that in the United States actually kills more people every year than AIDS, prostate cancer and breast cancer combined.

More commonly called “blood poisoning,” sepsis can quickly turn a modest infection into a whole-body inflammation, based on a dysfunctional immune response to endotoxins that are released from the cell walls of bacteria. When severe, this can lead to multiple organ failure and death.

When treatment is begun early enough, sepsis can sometimes be successfully treated with antibiotics. But they are not always effective and the mortality rate for the condition is still 28-50 percent. About one in every four people in a hospital emergency room is there because of sepsis, and millions of people die from it around the world every year, according to reports in the New England Journal of Medicine and other studies.

In pioneering research, OSU experts have used microchannel technology and special coatings to create a small device through which blood could be processed, removing the problematic endotoxins and preventing sepsis. Several recent professional publications have reported on their progress.

“More work remains to be done, and the support from the National Science Foundation will be instrumental in that,” said Adam Higgins, principal investigator on the grant and an assistant professor in the OSU School of Chemical, Biological and Environmental Engineering. “When complete, we believe this technology will treat sepsis effectively at low cost, or even prevent it when used as a prophylactic treatment.”

This technology may finally offer a way to tackle sepsis other than antibiotics, the researchers said.

“This doesn’t just kill bacteria and leave floating fragments behind, it sticks to and removes the circulating bacteria and endotoxin particles that might help trigger a sepsis reaction,” said Karl Schilke, the OSU Callahan Faculty Scholar in Chemical Engineering.

“We hope to emboss the device out of low-cost polymers, so it should be inexpensive enough that it can be used once and then discarded,” Schilke said. “The low cost would also allow treatment even before sepsis is apparent. Anytime there’s a concern about sepsis developing – due to an injury, a wound, an operation, or an infection – you could get ahead of the problem.”

“A big part of the problem with sepsis is that it moves so rapidly,” said Joe McGuire, professor and head of the OSU Department of Chemical, Biological and Environmental Engineering. “By the time it’s apparent what the problem is, it’s often too late to treat it.

“If given early enough, antibiotics and other treatments can sometimes, but not always, stop this process,” McGuire said. “Once these bacterial fragments are in the blood stream the antibiotics won’t always work. You can have successfully eradicated the living bacteria even as you’re dying.”

The approach being developed at the OSU College of Engineering is to move blood through a very small processor, about the size of a coffee mug, and literally grab the endotoxins and remove them.

Microchannels make this possible. They can provide accelerated heat and mass transfer as fluids move through tiny tubes the width of a human hair. Applications are already being studied in everything from heat exchangers to solar energy. They can be produced in mass quantity at low cost, stamped onto a range of metals or plastics, and used to process a large volume of liquid in a comparatively short time.

In the system developed at Oregon State, blood can be pumped through thousands of microchannels that are coated with what researchers call “pendant polymer brushes,” with repeating chains of carbon and oxygen atoms anchored on the surface. This helps prevent blood proteins and cells from sticking or coagulating. On the end of each pendant chain is a peptide – or bioactive agent – that binds tightly to the endotoxin and removes it from the blood, which then goes directly back to the patient.

Sepsis is fairly common. It can develop after an injury from an automobile accident, a dirty wound, an extended operation in a hospital that carries a risk of infection, or infectious illnesses in people with weak or compromised immune systems.

In the U.S., more than $20 billion was spent on this problem in 2011. It’s the single most expensive cause of health problems that require hospitalization.

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Adam Higgins, 541-737-6245

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Sepsis device

Sepsis device

Study links Greenland ice sheet collapse, sea level rise 400,000 years ago

CORVALLIS, Ore. – A new study suggests that a warming period more than 400,000 years ago pushed the Greenland ice sheet past its stability threshold, resulting in a nearly complete deglaciation of southern Greenland and raising global sea levels some 4-6 meters.

The study is one of the first to zero in on how the vast Greenland ice sheet responded to warmer temperatures during that period, which were caused by changes in the Earth’s orbit around the sun.

Results of the study, which was funded by the National Science Foundation, are being published this week in the journal Nature.

“The climate 400,000 years ago was not that much different than what we see today, or at least what is predicted for the end of the century,” said Anders Carlson, an associate professor at Oregon State University and co-author on the study. “The forcing was different, but what is important is that the region crossed the threshold allowing the southern portion of the ice sheet to all but disappear.

“This may give us a better sense of what may happen in the future as temperatures continue rising,” Carlson added.

Few reliable models and little proxy data exist to document the extent of the Greenland ice sheet loss during a period known as the Marine Isotope Stage 11. This was an exceptionally long warm period between ice ages that resulted in a global sea level rise of about 6-13 meters above present. However, scientists have been unsure of how much sea level rise could be attributed to Greenland, and how much may have resulted from the melting of Antarctic ice sheets or other causes.

To find the answer, the researchers examined sediment cores collected off the coast of Greenland from what is called the Eirik Drift. During several years of research, they sampled the chemistry of the glacial stream sediment on the island and discovered that different parts of Greenland have unique chemical features. During the presence of ice sheets, the sediments are scraped off and carried into the water where they are deposited in the Eirik Drift.

“Each terrain has a distinct fingerprint,” Carlson noted. “They also have different tectonic histories and so changes between the terrains allow us to predict how old the sediments are, as well as where they came from. The sediments are only deposited when there is significant ice to erode the terrain. The absence of terrestrial deposits in the sediment suggests the absence of ice.

“Not only can we estimate how much ice there was,” he added, “but the isotopic signature can tell us where ice was present, or from where it was missing.”

This first “ice sheet tracer” utilizes strontium, lead and neodymium isotopes to track the terrestrial chemistry.

The researchers’ analysis of the scope of the ice loss suggests that deglaciation in southern Greenland 400,000 years ago would have accounted for at least four meters – and possibly up to six meters – of global sea level rise. Other studies have shown, however, that sea levels during that period were at least six meters above present, and may have been as much as 13 meters higher.

Carlson said the ice sheet loss likely went beyond the southern edges of Greenland, though not all the way to the center, which has not been ice-free for at least one million years.

In their Nature article, the researchers contrasted the events of Marine Isotope Stage 11 with another warming period that occurred about 125,000 years ago and resulted in a sea level rise of 5-10 meters. Their analysis of the sediment record suggests that not as much of the Greenland ice sheet was lost – in fact, only enough to contribute to a sea level rise of less than 2.5 meters.

“However, other studies have shown that Antarctica may have been unstable at the time and melting there may have made up the difference,” Carlson pointed out.

The researchers say the discovery of an ice sheet tracer that can be documented through sediment core analysis is a major step to understanding the history of ice sheets in Greenland – and their impact on global climate and sea level changes. They acknowledge the need for more widespread coring data and temperature reconstructions.

“This is the first step toward more complete knowledge of the ice history,” Carlson said, “but it is an important one.”

Lead author on the Nature study is Alberto Reyes, who worked as a postdoctoral researcher for Carlson when both were at the University of Wisconsin-Madison. Carlson is now on the faculty in Oregon State’s College of Earth, Ocean, and Atmospheric Sciences.

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Anders Carlson, 541-737-3625; acarlson@coas.oregonstate.edu

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backpacks

Discovery of a bud-break gene could lead to trees adapted for a changing climate

CORVALLIS, Ore. — Scientists have confirmed the function of a gene that controls the awakening of trees from winter dormancy, a critical factor in their ability to adjust to environmental changes associated with climate change.

While other researchers have identified genes involved in producing the first green leaves of spring, the discovery of a master regulator in poplar trees (Populus species) could eventually lead to breeding plants that are better adapted for warmer climates.

The results of the study that began more than a decade ago at Oregon State University were published today in the Proceedings of the National Academy of Sciences, by scientists from Michigan Technological University and Oregon State.

“No one has ever isolated a controlling gene for this timing in a wild plant, outside of Arabidopsis, a small flowering plant related to mustard and cabbage,” said Steve Strauss, co-author and distinguished professor of forest biotechnology at OSU. “This is the first time a gene that controls the timing of bud break in trees has been identified.”

The timings of annual cycles — when trees open their leaves, when they produce flowers, when they go dormant — help trees adapt to changes in environmental signals like those associated with climate, but the genetics have to keep up, Strauss said.

While trees possess the genetic diversity to adjust to current conditions, climate models suggest that temperature and precipitation patterns in many parts of the world may expose trees to more stressful conditions in the future. Experts have suggested that some tree species may not be able to cope with these changes fast enough, whether by adaptation or migration. As a result, forest health may decline, trees may disappear from places they are currently found, and some species may even go extinct. 

“For example, are there going to be healthy and widespread populations of Douglas fir in Oregon in a hundred years?” said Strauss. “That depends on the natural diversity that we have and how much the environment changes. Will there be sufficient genetic diversity around to evolve populations that can cope with a much warmer and likely drier climate? We just don’t know.”

Strauss called the confirmation of the bud-break gene — which scientists named EBB1 for short — a “first step” in developing the ability to engineer adaptability into trees in the future.

“Having this knowledge enables you to engineer changes when they might become urgent,” he said.

Yordan Yordanov and Victor Busov at Michigan Tech worked with Cathleen Ma and Strauss at Oregon State to trace the function of EBB1 in buds and other plant tissues responsible for setting forth the first green shoots of spring. They developed modified trees that overproduced EBB1 genes and emerged from dormancy earlier in the year. They also showed that trees with less EBB1 activity emerged from dormancy later.

“The absence of EBB1 during dormancy allows the tree to progress through the physiological, developmental and adaptive changes leading to dormancy,” said Busov, “while the expression of EBB1 in specific cell layers prior to bud-break enables reactivation of growth in the cells that develop into shoots and leaves, and re-entry into the active growth phase of the tree.”

The study began when Strauss noticed poplar trees emerging earlier than others in an experimental field trial at Oregon State. One April morning, he found that four seedling trees in a 2.5-acre test plot were putting forth leaves at least a week before all the other trees. Strauss and Busov, a former post-doctoral researcher at Oregon State, led efforts to identify the genes responsible.

They found that EBB1 codes for a protein that helps to restart cell division in a part of the tree known as meristem, which is analogous to stem cells in animals. EBB1 also plays a role in suppressing genes that prepare trees for dormancy in the fall and in other processes such as nutrient cycling and root growth that are critical for survival. Altogether, they found nearly 1,000 other poplar genes whose activity is affected by EBB1.

It’s unlikely that plant breeders will use the finding any time soon, Strauss said. Breeders tend to rely on large clusters of genes that are associated with specific traits such as hardiness, tree shape or flowering. However, as more genes of this kind are identified, the opportunity to breed or engineer trees adapted to extreme conditions will grow.

Funding for the research was provided by the U.S. Department of Agriculture, the U.S. Department of Energy and the Tree Biosafety and Genomics Research Cooperative at Oregon State.

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Steve Strauss, 541-737-6578

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Tree research


Early flush

Early leaf flush

Findings point toward one of first therapies for Lou Gehrig’s disease

CORVALLIS, Ore. – Researchers have determined that a copper compound known for decades may form the basis for a therapy for amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

In a new study just published in the Journal of Neuroscience, scientists from Australia, the United States (Oregon), and the United Kingdom showed in laboratory animal tests that oral intake of this compound significantly extended the lifespan and improved the locomotor function of transgenic mice that are genetically engineered to develop this debilitating and terminal disease.

In humans, no therapy for ALS has ever been discovered that could extend lifespan more than a few additional months. Researchers in the Linus Pauling Institute at Oregon State University say this approach has the potential to change that, and may have value against Parkinson’s disease as well.

“We believe that with further improvements, and following necessary human clinical trials for safety and efficacy, this could provide a valuable new therapy for ALS and perhaps Parkinson’s disease,” said Joseph Beckman, a distinguished professor of biochemistry and biophysics in the OSU College of Science.

“I’m very optimistic,” said Beckman, who received the 2012 Discovery Award from the OHSU Medical Research Foundation as the leading medical researcher in Oregon.

ALS was first identified as a progressive and fatal neurodegenerative disease in the late 1800s and gained international recognition in 1939 when it was diagnosed in American baseball legend Lou Gehrig. It’s known to be caused by motor neurons in the spinal cord deteriorating and dying, and has been traced to mutations in copper, zinc superoxide dismutase, or SOD1. Ordinarily, superoxide dismutase is an antioxidant whose proper function is essential to life.

When SOD1 is lacking its metal co-factors, it “unfolds” and becomes toxic, leading to the death of motor neurons. The metals copper and zinc are important in stabilizing this protein, and can help it remain folded more than 200 years.

“The damage from ALS is happening primarily in the spinal cord and that’s also one of the most difficult places in the body to absorb copper,” Beckman said. “Copper itself is necessary but can be toxic, so its levels are tightly controlled in the body. The therapy we’re working toward delivers copper selectively into the cells in the spinal cord that actually need it. Otherwise, the compound keeps copper inert.”

“This is a safe way to deliver a micronutrient like copper exactly where it is needed,” Beckman said.

By restoring a proper balance of copper into the brain and spinal cord, scientists believe they are stabilizing the superoxide dismutase in its mature form, while improving the function of mitochondria. This has already extended the lifespan of affected mice by 26 percent, and with continued research the scientists hope to achieve even more extension.

The compound that does this is called copper (ATSM), has been studied for use in some cancer treatments, and is relatively inexpensive to produce.

“In this case, the result was just the opposite of what one might have expected,” said Blaine Roberts, lead author on the study and a research fellow at the University of Melbourne, who received his doctorate at OSU working with Beckman.

“The treatment increased the amount of mutant SOD, and by accepted dogma this means the animals should get worse,” he said. “But in this case, they got a lot better. This is because we’re making a targeted delivery of copper just to the cells that need it.

“This study opens up a previously neglected avenue for new disease therapies, for ALS and other neurodegenerative disease,” Roberts said.

Other collaborators on this research include OSU, the University of Melbourne, University of Technology/Sydney, Deakin University, the Australian National University, and the University of Leeds in the United Kingdom.

Funding has been provided by the Australian National Health and Medical Research Council, the U.S. National Institutes of Health, the Linus Pauling Institute and other groups in Australia and Finland.

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Joseph Beckman, 541-737-8867

Animal trapping records reveal strong wolf effect across North America

CORVALLIS, Ore. – Scientists have used coyote and red fox fur trapping records across North America to document how the presence of wolves influences the balance of smaller predators further down the food chain.

From Alaska and Yukon to Nova Scotia and Maine, the researchers have demonstrated that a “wolf effect” exists, favoring red foxes where wolves are present and coyotes where wolves are absent.

This effect requires that enough wolves be present to suppress coyotes over a wide area. Fur trapping records from Saskatchewan and Manitoba reveal that where wolves are absent in the southern agricultural regions of each province, coyotes outnumber foxes on average by 3-to-1. However, where wolves are abundant in the North, the balance swings dramatically in favor of foxes on average by 4-to-1 and at an extreme of 500-to-1 at one site.

In between is a 200-kilometer (124-mile) transition zone where too few wolves are present to tip the balance between coyotes and foxes.

The results of the study by Thomas Newsome and William Ripple in the Oregon State University Department of Forest Ecosystems and Society were published today in the Journal of Animal Ecology by the British Ecological Society.

“As wolves were extirpated across the southern half of North America, coyotes dramatically expanded their range,” said Newsome, a post-doctoral researcher. “They were historically located in the middle and western United States, but they dispersed all the way to Alaska in the early 1900s and to New Brunswick and Maine by the 1970s.”

“So essentially coyotes have been dispersing into wolf and red-fox range in the North but also into areas where wolves are absent but red fox are present in the East,” Newsome added.

Newsome came to the United States on a Fulbright scholarship from Australia where he earned a Ph.D. from the University of Sydney and specialized in the study of dingoes, that continent’s top predator. There’s a debate among Australians, he said, about the potential role of dingoes in suppressing introduced pests that have already decimated wildlife there.

“Over the last 200 years, Australia has had the highest extinction rate in the world,” Newsome said. “The debate is about whether the dingo can provide positive ecological benefits. Where dingoes have been removed, the impacts of introduced red foxes and feral cats have been quite severe on native fauna.”

Dingoes are managed as a pest in New South Wales, the country’s most populous state. To reduce dingo predation in the livestock industry, Australia also maintains the world’s longest fence, which runs for 5,500 kilometers (3,400 miles) in an attempt to exclude dingoes from almost a quarter of the continent.

In North America, the effect of wolves on coyotes and red foxes provides a natural case study that can be instructive for Australians. “Australians can learn a lot from how wolves are managed in North America, and Americans can learn from the ecological role of the dingo,” Newsome said.

As coyotes have expanded in North America, they have become a major cause of concern for the livestock industry. In the United States in 2004, researchers estimated annual losses due to coyote predation on sheep and cattle at $40 million. To reduce those damages, the Wildlife Service of the U.S. Department of Agriculture has a program to reduce coyote numbers, an effort that has drawn criticism from conservation groups.

In reviewing the fur trapping data from two U.S. and six Canadian jurisdictions, Newsome and Ripple eliminated potential sources of bias such as records from fur farms that raise foxes. The fur prices of coyotes and red foxes are also strongly correlated, and the two species occupy much of the same types of habitat, so they are equally likely to be targeted and caught in hunters’ traps.

“This study gives us a whole other avenue to understand the ecological effects of wolves on landscapes and animal communities,” said Ripple. He has studied the influence of carnivores on their prey — such as deer and elk — and on vegetation from aspen trees to willows. He and his colleagues have shown that the removal of top predators can cause dramatic shifts within ecosystems.

Wolves are naturally recolonizing many areas of the United States following their reintroduction into Yellowstone National Park and surrounding areas in 1995. Scientists are studying wolf interactions with other species, and in particular, there is interest in determining whether recolonizing wolves will suppress coyote populations and have cascading effects on red foxes and other species.

Newsome received funding from the Australian-American Fulbright Commission and from the government and universities of New South Wales in Australia.

 

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Thomas Newsome, 541-737-3197

Wiliam Ripple, 541-737-3056

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Coyote (Photo: Shawn McCready)

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Red fox (Photo: Kelly Colgan Azar)

Gray Wolf, credit- Doug McLaughlin copy 2

Gray wolf (Photo: Doug McLaughlin)

ODFW, OSU to survey hunters about use of lead ammunition

CORVALLIS, Ore. – The Oregon Department of Fish and Wildlife and Oregon State University are collaborating on an effort to survey Oregon hunters about their use and knowledge of lead ammunition.

The random sample of 4,200 Oregon hunters will begin later this month and those selected should receive a letter from ODFW within the next two weeks. Oregon has approximately 250,000 hunters and the survey will include hunters from each geographic region of the state.

The use of lead ammunition has become a national issue because of impacts to wildlife and human health concerns, according to Ron Anglin, ODFW Wildlife Division administrator. Last year, California passed a law banning the use of lead ammunition for all hunting in the state beginning in 2019; other states have adopted voluntary measures encouraging the use of ammunition made from alternative compounds.

“There is no proposal to ban or limit use of lead ammunition in Oregon, but developments outside of Oregon could affect the use of lead ammunition within the state,” Anglin said. “The Environmental Protection Agency was petitioned to ban the use of lead in ammunition on a nationwide basis and there is the potential of condors being restored in northern California.”

The California legislature passed a law banning lead ammunition to protect endangered California condors, according to Dana Sanchez, an OSU Extension wildlife specialist and one of the project leaders. Condors can become ill after scavenging on animals that have been killed by lead bullets. The birds ingest lead fragments and can become sick or die, she said.

“Historically, Oregon has had condors, though none are known to live here now,” Sanchez pointed out. “However, there are efforts to re-establish populations in northern California and if they are successful, it is only a matter of time before condors begin frequenting the southern portions of Oregon.

“Once condors appear in Oregon, they would be subject to federal protection under the Endangered Species Act,” she added.

Sanchez said some conservation organizations in the state are monitoring lead levels in birds of prey brought into wildlife rehabilitation centers. There is increasing concern that lead exposure may be causing impacts to raptors and eagles in some areas, she said.

“This could lead to an initiative or other efforts to eliminate or restrict the use of lead ammunition,” Sanchez said.

The survey was developed by the OSU Survey Research Center, which will collect the data for ODFW and the OSU Wildlife Extension program. Survey results will be used to inform discussions among agencies, groups and others about any potential restrictions in the use of lead ammunition.

The purpose of the survey, Anglin said, is to gather information from the group of stakeholders who would be most affected by any restrictions on lead ammunition – Oregon hunters.

“Ideally, we would like to survey all Oregon hunters, but that is expensive,” Anglin said. “However, by selecting a random sample of hunters from regions across the state, we should get a clear picture of how Oregon hunters feel about lead ammunition and possible alternatives.”

Persons not chosen for the survey are welcome to provide comments on lead ammunition directly to the Oregon Department of Fish & Wildlife at a special email address: ODFW.wildlifeinfo@state.or.us

Anglin said the ODFW/OSU project team plans to conduct a similar survey of non-hunting Oregonians in the future.

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Ron Anglin, 503-947-6301; ODFW.wildlifeinfo@state.or.us; Dana Sanchez, 541-737-6003; dana.sanchez@oregonstate.edu

Technology using microwave heating may impact electronics manufacture

The study this story is based on is available online: http://bit.ly/1pJjhnK

 

CORVALLIS, Ore. – Engineers at Oregon State University have successfully shown that a continuous flow reactor can produce high-quality nanoparticles by using microwave-assisted heating – essentially the same forces that heat up leftover food with such efficiency.

Instead of warming up yesterday’s pizza, however, this concept may provide a technological revolution.

It could change everything from the production of cell phones and televisions to counterfeit-proof money, improved solar energy systems or quick identification of troops in combat.

The findings, recently published in Materials Letters, are essentially a “proof of concept” that a new type of nanoparticle production system should actually work at a commercial level.

“This might be the big step that takes continuous flow reactors to large-scale manufacturing,” said Greg Herman, an associate professor and chemical engineer in the OSU College of Engineering. “We’re all pretty excited about the opportunities that this new technology will enable.”

Nanoparticles are extraordinarily small particles at the forefront of advances in many biomedical, optical and electronic fields, but precise control of their formation is needed and “hot injection” or other existing synthetic approaches are slow, costly, sometimes toxic and often wasteful.

A “continuous flow” system, by contrast, is like a chemical reactor that moves constantly along. It can be fast, cheap, more energy-efficient, and offer lower manufacturing cost. However, heating is necessary in one part of the process, and in the past that was best done only in small reactors.

The new research has proven that microwave heating can be done in larger systems at high speeds. And by varying the microwave power, it can precisely control nucleation temperature and the resulting size and shape of particles.

“For the applications we have in mind, the control of particle uniformity and size is crucial, and we are also able to reduce material waste,” Herman said. “Combining continuous flow with microwave heating could give us the best of both worlds – large, fast reactors with perfectly controlled particle size.”

The researchers said this should both save money and create technologies that work better. Improved LED lighting is one possibility, as well as better TVs with more accurate colors. Wider use of solid state lighting might cut power use for lighting by nearly 50 percent nationally. Cell phones and other portable electronic devices could use less power and last longer on a charge.

The technology also lends itself well to creation of better “taggants,” or compounds with specific infrared emissions that can be used for precise, instant identification – whether of a counterfeit $20 bill or an enemy tank in combat that lacks the proper coding.

In this study, researchers worked with lead selenide nanoparticles, which are particularly good for the taggant technologies. Other materials can be synthesized using this reactor for different applications, including copper zinc tin sulfide and copper indium diselenide for solar cells.

New Oregon jobs and businesses are already evolving from this work.

OSU researchers have applied for a patent on aspects of this technology, and are working with private industry on various applications. Shoei Electronic Materials, one of the collaborators, is pursuing “quantum dot” systems based on this approach, and recently opened new manufacturing facilities in Eugene, Ore., to use this synthetic approach for quantum dot enabled televisions, smartphones and other devices.

The research has been supported by the Air Force Research Laboratory, OSU Venture Funds, and the Oregon Nanoscience and Microtechnologies Institute, or ONAMI.

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Greg Herman, 541-737-2496

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Continuous flow reactor

Continuous flow reactor

Statin use associated with less physical activity

CORVALLIS, Ore. – One of the longest studies of its type has found that use of statins in older men is associated with less physical activity, a significant issue for a population that’s already sedentary.

The findings, published today in JAMA Internal Medicine, raise concerns about a decline in much-needed physical activity among men who take some of the most widely prescribed medications in the world. Almost one-third of older Americans take statins, usually to reduce their cholesterol levels.

The research did not identify why men who took statins exercised less – it just confirmed that they did. Possible causes include the muscle pain that can be a side effect of statin use, and also disruption of the mitochondrial function in cells, which could contribute to fatigue and muscle weakness.

Physical activity in older adults helps to maintain a proper weight, prevent cardiovascular disease and helps to maintain physical strength and function,” said David Lee, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author of the study.

“We’re trying to find ways to get older adults to exercise more, not less,” Lee said. “It’s a fairly serious concern if use of statins is doing something that makes people less likely to exercise.”

Muscle pain is found in 5-30 percent of people who take statins, Lee said, and some people also report feeling less energetic, weak or tired.

In an analysis of 3,071 community-living men, age 65 or older, from six geographic regions in the United States, researchers found that men who took statins averaged about 40 minutes less of moderate physical activity over a one-week period, compared to those who weren’t taking the medication.

That would equate to the loss of 150 minutes a week of slow-paced walking, Lee said.

“For an older population that’s already pretty sedentary, that’s a significant amount less exercise,” he said. “Even moderate amounts of exercise can make a big difference.”

Of some significance, the study also found that new statin users had the largest drop in physical activity. An increase in sedentary behavior, which is associated with all-cause mortality and also death from cardiovascular disease, was also observed in statin users.

Some previous studies with older adults and statins had found similar results, but those analyses were short-term. This research followed men for almost seven years after initial baseline studies were done, and compared changes in physical activity among users and non-users of statins. In parts of the experiments, men wore accelerometers for a week to track by the minute their level of activity.

“Given these results, we should be aware of a possible decrease in physical activity among people taking a statin,” Lee said.

“This could decrease the benefit of the medication,” he said. “If someone is already weak, frail, or sedentary, they may want to consider this issue, and consult with their doctor to determine if statin use is still appropriate.”

This study was done with older men, and generalization of the findings to older women may not be appropriate, the researchers noted in their study.

The research was done by scientists from OSU; the Oregon Health & Science University; the Department of Veterans Affairs Medical Center in Portland, Ore.; the California Pacific Medical Center Research Institute in San Francisco; the Stanford Prevention Research Center; and the Department of Medicine at the University of California.

The study was supported by the National Institutes of Health and the Medical Research Foundation of Oregon.

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David Lee, 503-494-2258

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Maintaining activity levels

Maintaining activity

Research could lead to new cancer assay, aid both dogs and humans

CORVALLIS, Ore. – Veterinary researchers at Oregon State University have identified a unique group of proteins that indicate the presence of transitional cell carcinoma – the most common cause of bladder cancer – and may lead to a new assay which could better diagnose this disease in both dogs and humans.

Bladder cancer is particularly common in some dog breeds, such as collies, sheepdogs and terriers, but is rarely diagnosed in animals before it has spread significantly. Some assays exist to detect it in humans, but they often have a high-number of false-positive identifications.

An improved assay to detect this serious disease much earlier in both animals and humans should be possible, scientists said, and may even become affordable enough that it could be used as an over-the-counter product to test urine, much like a human pregnancy test. Some of the work may also contribute to new therapies, they said.

“Research of this type should first help us develop a reliable assay for this cancer in dogs, and improve the chance the disease can be caught early enough that treatments are effective,” said Shay Bracha, an assistant professor in the OSU College of Veterinary Medicine.

“However, this type of cancer is essentially the same in dogs and humans,” Bracha said. “Dogs are an excellent model for human cancer research, and an assay that works with dogs should be directly relevant to creation of a similar assay for humans. We hope to make it inexpensive and convenient, something that people could use routinely to protect either the health of their pets or themselves.”

The findings were published recently in Analytical Chemistry, a professional journal.

In this research, scientists used mass spectrometry and the evolving science of proteomics to identify 96 proteins that appear related to transitional cell carcinoma. This is a fairly common cancer in dogs, often as a result of exposure to pesticides, herbicides, and poor quality foods; and in humans is closely related to smoking.

Advanced-stage disease in both dogs and humans has a poor prognosis, as chemotherapy and radiation treatments are often ineffective. Average survival time is less than one year. Some assays exist to help identify the disease in humans but can produce false positive results, often as a result of urinary tract infections. And the biopsies used to make a definitive diagnosis require general anesthesia and also run the risk of actually spreading the disease.

The group of proteins identified in this research already have a 90 percent accuracy, and researchers say they hope to improve upon that with continued research.

However, researchers say that some of these proteins are more than just biomarkers of the disease – they are part of the disease process. Identifying proteins that are integral to the spread of the cancer may allow new targets for intervention and cancer therapies, they said.

Collaborators on this research included the OSU Department of Chemistry. A mathematical model that was integral to the study was created by Jan Medlock, an OSU assistant professor of veterinary medicine, and veterinary researchers Michael McNamara and Ian Hilgart helped initiate the project. The work was supported in part by the National Institutes of Health.

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Shay Bracha, 541-737-4844

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Border collie

Border collie