The work, presented online May 27 in Nature Geoscience, shows that once the angle of a slope exceeds 30 degrees – whether from uplift, a rushing stream carving away the bottom of the slope or a combination of the two – landslide erosion increases significantly until the hillside stabilizes.

The Landsat satellite image at left shows a huge lake on the Tsangpo River behind a dam created by a landslide (in red, lower right of the lake) in early 2000. The image at right shows the river following a catastrophic breach of the dam in June 2000.

U.S. Geological Survey/NASA

"I think the formation of these landscapes could apply to any steep mountain terrain in the world," said lead author Isaac Larsen, a University of Washington doctoral student in Earth and space sciences.

The study, co-authored by David Montgomery, a UW professor of Earth and space sciences and Larsen's doctoral adviser, focuses on landslide erosion along rivers in the eastern Himalaya region of southern Asia.

The scientists studied images of more than 15,000 landslides before 1974 and more than 550 more between 1974 and 2007. The data came from satellite imagery, including high-resolution spy satellite photography that was declassified in the 1990s.

They found that small increases in slope angle above about 30 degrees translated into large increases in landslide erosion as the stress of gravity exceeded the strength of the bedrock.

"Interestingly, 35 degrees is about the same angle that will form if sand or other coarse granular material is poured into a pile," Larsen said. "Sand is non-cohesive, whereas intact bedrock can have high cohesion and should support steeper slopes.

"The implication is that bedrock in tectonically active mountains is so extensively fractured that in some ways it behaves like a sand pile. Removal of sand at the base of the pile will cause miniature landslides, just as erosion of material at the base of hill slopes in real mountain ranges will lead to landslides."

The researchers looked closely at an area of the 150-mile Tsangpo Gorge in southeast Tibet, possibly the deepest gorge in the world, downstream from the Yarlung Tsangpo River where the Po Tsangpo River plunges more than 6,500 feet, about 1.25 miles. It then becomes the Brahmaputra River before flowing through the Ganges River delta and into the Bay of Bengal.

Map by Wikimedia Commons user Pfly.

The scientists found that within the steep gorge, the rapidly flowing water can scour soil from the bases, or toes, of slopes, leaving exposed bedrock and an increased slope angle that triggers landslides to stabilize the slopes.

From 1974 through 2007, erosion rates reached more than a half-inch per year along some 6-mile stretches of the river within the gorge, and throughout that active landslide region erosion ranged from 0.15 to 0.8 inch per year. Areas with less tectonic and landslide activity experienced erosion rates of less than 0.15 inch a year.

Images showed that a huge landslide in early 2000 created a gigantic dam on a stretch of the Po Tsangpo. The dam failed catastrophically in June of that year, and the ensuing flood caused a number of fatalities and much property damage downstream.

That event illustrates the processes at work in steep mountain terrain, but the processes happen on a faster timescale in the Tsangpo Gorge than in other steep mountain regions of the world and so are more easily verified.

"We've been able to document the role that landslides play in the Tsangpo Gorge," Larsen said. "It explains how steep mountain topography evolves over time."

The work was financed by NASA, the Geological Society of America, Sigma Xi (the Scientific Research Society) and the UW Quaternary Research Center and Department of Earth and Space Sciences.

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For more information, contact Larsen at 206-265-0473 or larseni@uw.edu, or Montgomery at 206-685-2560 or dave@ess.washington.edu.

A University of Washington mathematician is part of an international team working to understand invisibility and extend its possible applications. The group has now devised an amplifier that can boost light, sound or other waves while hiding them inside an invisible container.

"You can isolate and magnify what you want to see, and make the rest invisible," said corresponding author Gunther Uhlmann, a UW mathematics professor. "You can amplify the waves tremendously. And although the wave has been magnified a lot, you still cannot see what is happening inside the container.”

The findings are published online this week in the Proceedings of the National Academy of Sciences.

As a first application, the researchers propose manipulating matter waves, which are the mathematical description of particles in quantum mechanics. The researchers envision building a quantum microscope that could capture quantum waves, the waves of the nanoworld. A quantum microscope could, for example, be used to monitor electronic processes on computer chips.

The authors dubbed their system "Schrödinger's hat," referring to the famed Schrödinger's cat in quantum mechanics. The name is also a nod to the ability to create something from what appears to be nothing.

"In some sense you are doing something magical, because it looks like a particle is being created. It's like pulling something out of your hat," Uhlmann said.

Matter waves inside the hat can also be shrunk, though Uhlmann notes that concealing very small objects "is not so interesting."

A matter wave hitting a Schrodinger's hat. The wave inside the container is magnified. Outside, the waves wrap as if they had never encountered any obstacle.

G. Uhlmann, U. of Washington

Uhlmann, who is on leave at the University of California, Irvine, has been working on invisibility with fellow mathematicians Allan Greenleaf at the University of Rochester, Yaroslav Kurylev at University College London in the U.K., and Matti Lassas at the University of Helsinki in Finland, all of whom are co-authors on the new paper.

The team helped develop the original mathematics to formulate cloaks, which must be realized using a class of engineered materials, dubbed metamaterials, that bend waves so that it appears as if there was no object in their path. The international team in 2007 devised wormholes in which waves disappear in one place and pop up somewhere else.

For this paper, they teamed up with co-author Ulf Leonhardt, a physicist at the University of St. Andrews in Scotland and author on one of the first papers on invisibility.

Recent progress suggests that a Schrodinger’s hat could, in fact, be built for some types of waves.

"From the experimental point of view, I think the most exciting thing is how easy it seems to be to build materials for acoustic cloaking," Uhlmann said. Wavelengths for microwave, sound and quantum matter waves are longer than light or electromagnetic waves, making it easier to build the materials to cloak objects from observation using these phenomena.

"We hope that it's feasible, but in science you don't know until you do it," Uhlmann said. Now that the paper is published, they hope to find collaborators to build a prototype.

The research was funded by the National Science Foundation in the U.S., the Engineering and Physical Sciences Research Council and the Royal Society in the U.K., and the Academy of Finland.

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For more information, contact Uhlmann at 206-543-1946 or gunther@math.washington.edu. He will be out of the country starting Wednesday, May 30 and best reached via email. Uhlmann is on leave at UC Irvine through the end of June.

University of Washington bioengineers have developed the first structure to grow small human blood vessels, creating a 3-D test bed that offers a better way to study disease, test drugs and perhaps someday grow human tissues for transplant.

The findings are published online this week in the Proceedings of the National Academy of Sciences.

"In clinical research you just draw a blood sample," said first author Ying Zheng, a UW research assistant professor of bioengineering. "But with this, we can really dissect what happens at the interface between the blood and the tissue. We can start to look at how these diseases start to progress and develop efficient therapies."

Researchers made a functional microvessel that spells the letters "UW." The white bar measures 100 micrometers, about the width of a human hair.

Y. Zheng, U. of Washington

During a period of two weeks, the endothelial cells grew throughout the structure and formed tubes through the mold's rectangular channels, just as they do in the human body.

When brain cells were injected into the surrounding gel, the cells released chemicals that prompted the engineered vessels to sprout new branches, extending the network. A similar system could supply blood to engineered tissue before transplant into the body.

After joining the UW last year, Zheng collaborated with the Puget Sound Blood Center to see how this research platform would work to transport real blood.

Engineered microvessels can form bends and T-junctions, like this one. The blue dots are the nuclei of the cells in the vessel walls, and the red lines are the cell junctions. Smooth muscle cells (green) wrap and tighten around the vessels, just as they do in the human body.

Y. Zheng, U. of Washington

The engineered vessels could transport human blood smoothly, even around corners. And when treated with an inflammatory compound the vessels developed clots, similar to what real vessels do when they become inflamed.

The system also shows promise as a model for tumor progression. Cancer begins as a hard tumor but secretes chemicals that cause nearby vessels to bulge and then sprout. Eventually tumor cells use these blood vessels to penetrate the bloodstream and colonize new parts of the body.

When the researchers added to their system a signaling protein for vessel growth that's overabundant in cancer and other diseases, new blood vessels sprouted from the originals. These new vessels were leaky, just as they are in human cancers.

"With this system we can dissect out each component or we can put them together to look at a complex problem. That's a nice thing—we can isolate the biophysical, biochemical or cellular components. How do endothelial cells respond to blood flow or to different chemicals, how do the endothelial cells interact with their surroundings, and how do these interactions affect the vessels' barrier function? We have a lot of degrees of freedom," Zheng said.

The system could also be used to study malaria, which becomes fatal when diseased blood cells stick to the vessel walls and block small openings, cutting off blood supply to the brain, placenta or other vital organs.

"I think this is a tremendous system for studying how blood clots form on vessels walls, how the vessel responds to shear stress and other mechanical and chemical factors, and for studying the many diseases that affect small blood vessels," said co-author Dr. José López, a professor of biochemistry and hematology at UW Medicine and chief scientific officer at the Puget Sound Blood Center.

Future work will use the system to further explore blood vessel interactions that involve inflammation and clotting. Zheng is also pursuing tissue engineering as a member of the UW's Center for Cardiovascular Biology and the Institute for Stem Cell and Regenerative Medicine.

Other co-authors are UW physics senior Samuel Totorica; Abraham Stroock, Michael Craven, Nak Won Choi, Michael Craven, Anthony Diaz-Santana and Claudia Fischbach at Cornell; Junmei Chen at the Puget Sound Blood Center; and Barbara Hempstead at Weill Cornell Medical College.

The research was funded by the National Institutes of Health, the American Heart Association, the Human Frontier Science Program and Cornell University.

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For more information, contact Zheng at 206-543-3223 or yingzy@uw.edu.

Determining the proper time to flower, important if a plant is to reproduce successfully, involves a sequence of molecular events, a plant's circadian clock and sunlight.

Understanding how flowering works in the simple plant used in this study – Arabidopsis  – should lead to a better understanding of how the same genes work in more complex plants grown as crops such as rice, wheat and barley, according to Takato Imaizumi, a University of Washington assistant professor of biology and corresponding author of a paper in the May 25 issue of the journal Science.

"If we can regulate the timing of flowering, we might be able to increase crop yield by accelerating or delaying this. Knowing the mechanism gives us the tools to manipulate this," Imaizumi said. Along with food crops, the work might also lead to higher yields of plants grown for biofuels.

At specific times of year, flowering plants produce a protein known as Flowering Locus T in their leaves that induces flowering. Once this protein is made, it travels from the leaves to the shoot apex, a part of the plant where cells are undifferentiated, meaning they can either become leaves or flowers. At the shoot apex, this protein starts the molecular changes that send cells on the path to becoming flowers.

Changes in day length tell many organisms that the seasons are changing. It has long been known that plants use an internal time-keeping mechanism known as the circadian clock to measure changes in day length. Circadian clocks synchronize biological processes during 24-hour periods in people, animals, insects, plants and other organisms.

Imaizumi and the paper's co-authors investigated  what's called the FKF1 protein, which they suspected was a key player in the mechanism by which plants recognize seasonal change and know when to flower. FKF1 protein is a photoreceptor, meaning it is activated by sunlight.

Takato Imaizumi and Young Hun Song in the Takato plant lab at the University of Washington.

U of Washington

"The FKF1 photoreceptor protein we've been working on is expressed in the late afternoon every day, and is very tightly regulated by the plant's circadian clock," Imaizumi said. "When this protein is expressed during days that are short, this protein cannot be activated, as there is no daylight in the late afternoon. When this protein is expressed during a longer day, this photoreceptor makes use of the light and activates the flowering mechanisms involving Flowering Locus T. The circadian clock regulates the timing of the specific photoreceptor for flowering. That is how plants sense differences in day length."

This system keeps plants from flowering when it's a poor time to reproduce, such as the dead of winter when days are short and nights are long.

The new findings come from work with the plant Arabidopsis, a small plant in the mustard family that's often used in genetic research. They validate predictions from a mathematical model of the mechanism that causes Arabidopsis to flower that was developed by Andrew Millar, a University of Edinburgh professor of biology and co-author of the paper.

"Our mathematical model helped us to understand the operating principles of the plants' day-length sensor," Millar said. "Those principles will hold true in other plants, like rice, where the crop's day-length response is one of the factors that limits where farmers can obtain good harvests. It's that same day-length response that needs controlled lighting for laying chickens and fish farms, so it's just as important to understand this response in animals.

"The proteins involved in animals are not yet so well understood as they are in plants but we expect the same principles that we've learned from these studies to apply."

First author on the paper is Young Hun Song, a postdoctoral researcher in Imaizumi's UW lab. The other co-authors are Benjamin To, who was a UW undergraduate student when this work was being conducted, and Robert Smith, a University of Edinburgh graduate student. The work was funded by the National Institutes of Health, and the United Kingdom's Biotechnology and Biological Sciences Research Council.

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For more information:
Imaizumi, 206-543-8709, takato@uw.edu

The goals of the UW Research Affiliates Program on Transporters are twofold. First, it will provide quantitative information on drug transporters. The data  would help better predict the fate of new drugs early in development and thereby expedite the movement of promising drugs  into clinical trials. Second, the findings would enhance the collective knowledge about personalized medicine by better predicting the potential for drug-drug interactions and by showing how an individual’s genetics might influence the processing of  certain drugs.

A nucleoside transporter is expressed at the plasma and the mitochondrial membrane in cells.

The program's researchers hope to achieve these aims by studying and measuring the drug transporters produced in various human tissues and cells. Transporters are membrane proteins in tissues. They help the body absorb, distribute, metabolize and excrete drugs. Such transporters exist throughout the body, including in the liver, kidney, red blood cells and the brain.

For more than a decade, Unadkat’s lab has studied drug transporters in the disposition, efficacy and toxicity of drugs such as those used in the treatment of hepatitis C and HIV infection. Before translating findings from this in-vitro research (done in the test tube) to in-vivo studies (those conducted in the body), Unadkat realized additional research was required. He wanted to know more about the amount and type of transporters present in human tissues.

“Recognizing this gap in knowledge, our lab embarked on setting up a program a few years ago to quantify the level of expression of transporters in human tissues,” said Unadkat.

To do so, he set up a collaboration with Yurong Lai, a Pfizer scientist and a former postdoctoral fellow of the Unadkat Lab.Their novel approach links mass spectrometry (an analytical technique that identifies chemicals by their mass and charge) with liquid chromatography (an analytical technique for separating ions or molecules that are dissolved in a solvent). Seed funding for this work came from Pfizer.

Over time, Unadkat wanted to find a way to share collective expertise and resources with others in the industry who were conducting similar research. He began discussions with scientists from across the pharmaceutical research industry. With the help of two UW offices that help facilitate academia-industry partnerships and help secure support for sponsored collaborations — the UW Center for Commercialization and the UW Office of Sponsored Programs — UW Research Affiliates Program on Transporters came into being late last year with the three major research companies on board. Additional discussions are under way with other companies that have expressed interest in joining the initiative.

This two-part human brain scan shows the transporter-mediated distribution of a drug in the presence and absence of a transporter inhibitor.

Through the initiative, Unadkat, lead scientist Bhagwat Prasad and other scientists and graduate students in the Unadkat Lab are measuring expression of transporters in human tissues and in other kinds of cells and tissues sent from pharmaceutical companies. Members of the program will communicate their results and next steps through regular online and in-person meetings and through online access to the data generated by the Unadkat Lab. This kind of collaboration will mark a first for the companies..

“Such multi-company collaboration is rare because pharmaceutical companies are competitors,” said Unadkat. “Astrazeneca, Genentech and Merck were willing to collaborate and fund UWRAPT because the research is not proprietary.”

In fact, the information that comes from the program's research will benefit the School of Pharmacy and all the companies involved in drug-development research. All data generated by the program will be shared with all three companies and eventually be published.

What’s more, the UW Research Affiliates Program on Transporters partnership will help the School of Pharmacy train future scientists in pharmaceutical research. The program is intended to be a multi-year, public-private collaborative research venture.

Ultimately, Unadkat and his colleagues hope that by improving understanding about the quantity and types of transporters expressed in human tissues, they will advance the collective knowledge about how medicines are processed by the body. In turn, this will help health care providers prevent drug interactions and understand how genetics affects the way individuals process medications.

Pediatrician James Stout is an innovator in long-distance training of health professionals.

Asthma and chronic obstructive pulmonary disease are common medical problems, especially among low-income and minority populations. These groups have more severe cases of these lung diseases and a greater number of hospitalizations because of their illness.

“My view is that anyone with either of these diagnoses deserves the test as part of their overall assessment,” Stout said, who also is a pediatrician at the Odessa Brown Children’s Clinic, a satellite of Seattle Children’s Hospital located in the Central District.

He pointed to other studies revealing that up to 65 percent of general pediatricians do not use spirometry in routine asthma care. Even when spirometry is performed in primary-care doctor’s offices, many of the tests don’t meet American Thoracic Society quality standards, research has indicated.

Usually sprirometry is taught hands-on, with an experienced provider demonstrating how it’s done, letting trainees try it and interpret the results, and then coaching the trainees until they consistently perform it correctly.

However, in-person training is inconvenient for some providers to obtain. Practicing primary-care providers in rural areas have long travel distances to teaching sites, and those working in physician shortage areas or in safety-net practices for vulnerable populations are reluctant to spare time from their patients.

Stout and his group devised a multimedia online training that primary-care professionals in pediatrics, family medicine and internal medicine, as well as their support staff, typically nurses and medical assistants, can take in their offices. The Web-based training is followed by several weeks of ongoing coaching. Health care professionals can hook up one brand of spirometers to a secure system that transmits the results, without any information that identifies the patient, to experts who check for problems in the healthcare professional’s technique.

A spirometer for testing lung function in asthma and emphysema and before-and-after smoking cessation.

EasyOne

Spirometry training can be put to use in other ways in primary care practices. For example, it could be performed as part of a smoking cessation program. Patients may then be motivated to continue to abstain from tobacco as they watch their lung function get better over time.

A paper recently published in Academic Pediatrics evaluating the training for health professionals shows that it translates to better asthma care for patients.  Stout's team has since refined the approach and delivered it to more than 250 practices in a score of states. Ongoing technical improvements, he said, has made the training more user-friendly.

“The program we deliver now, Spirometry 360, is both shorter and better than the one we tested in the trial,” Stout said.

Does the online education in spirometry translate to better health for asthma patients? As part of Stout’s research team, Dr. Rita Mangione-Smith, professor of pediatrics, Division of General Pediatrics, has been leading a study to see if the online training improves health outcomes for children with asthma. The preliminary findings are positive; final results should be available later this year. Mangione-Smith is also a scientist at the Seattle Children’s Research Institute.

“Even though traditionally these types of hands-on skills are taught in person,” Stout said, “our team has proven that this procedure can be learned successfully over long distance and that this training improved asthma care in the pediatric practices we studied.”

This latest development in long-distance spirometry training may pave the way for teaching other sophisticated procedures over the miles through advances in learning technology and telecommunications. The University of Washington has licensed this particular approach to remote medical training as Spirometry 360.

The Academic Pediatric paper evaluating the effectiveness of remote teaching of spirometry is “Learning from a Distance: Spirometry Training in Improving Asthma Care.”  In addition to Stout and Mangione-Smith, other UW and Seattle Children’s Research Institute investigators on the study were Drs. Karen Smith, Chuan Zhou, Cam Solomon and Michelle M. Garrison. Dr. Allen Dozer from New York Medical College in Valhalla was also part of the study team.

A federal Agency for Healthcare Research and Quality grant funded the study.

Organized by staff with Conservation Magazine and the University of Washington Department of Biology, the event is meant to appeal to a mix of students, scientists and other citizens of Puget Sound.

"We want people to come away from this event with a sense that conservation isn't just about stopping bad things from happening, but also about starting good things. They will get a glimpse of the kind of environmental innovations that are possible when we include engineers, architects, cooks and entrepreneurs in the environmental conversation," said Estella Leopold, UW professor emeritus of biology and an event host. "It turns out that environmental inspiration can be found in the most unexpected places."

The event will be from 10 a.m. to 4 p.m. Saturday, June 2, at Seattle's Town Hall and will feature 11 speakers talking about food, agriculture, built environments, energy, technology and business. Two are from the UW, the rest are with other U.S. and European institutions and organizations. Veteran science journalists David Malakoff with Science magazine and John Nielsen, a former environmental correspondent with National Public Radio, will guide discussions audience discussions.

"This event is not only about listening to the speakers – it’s also about listening to the audience," said Dee Boersma, UW professor of biology and co-organizer of the event. For example, Earthfix, a media project of Northwest public radio and television stations, will host a digital story booth where participants can share their thoughts and stories about environmental issues.

Now is the time for this kind of regional event, Boersma said.

"The Puget Sound region and the UW are emerging hubs for environmental innovation," she said. "We have a tremendous combination of interests and expertise here—environmental concern, technological know-how, and business entrepreneurship. This event mixes these communities up and brings smart people together to imagine a greener future."

Winter 2012 edition

Tickets can be purchased online for $50 – $25 for students– and include a catered lunch and a one-year subscription to Conservation Magazine, a quarterly UW publication distributed in 58 countries. There will be a limited number of tickets available at the door.

Major sponsors of the event with Conservation Magazine are the Bullitt Foundation, John D. and Catherine T. MacArthur Foundation, UW College of Arts and Sciences and UW College of the Environment. Fifteen other UW and community organizations are partners.

"Just as TED originally brought to the web ideas worth spreading about technology, entertainment and design, we hope to launch something similar for the environment," said UW's Kathryn Kohm, editor of Conservation Magazine and the other co-organizer of the remix event.

For more information contact Lindsey Doermann, doermann@uw.edu, 206-221-5292.

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For more information, news media can contact:
Boersma, 206-616-2185, boersma@uw.edu
Kohm, 206-685-4724, kkohm@uw.edu

A Tokyo museum book contains page after page of the strings of DNA code letters A,G,C and T found in the human genome. A single letter change might influence health risks.

Ben Casey

“This is a dramatic example of how recent human history has profoundly shaped patterns of genetic variation,” said Joshua Akey, University of Washington associate professor of genome sciences and a senior author of the study. His lab studies the genetic architecture behind differences among humans (as well as among other species) and the mechanisms of evolutionary change.

Although so-called single nucleotide variants are rare, they may influence a person’s resistance or susceptibility to common diseases, like heart or lung trouble or blood problems. The rarity of each specific variation means that scientists will often need to study DNA samples from very large numbers of people to draw any genetic links to these disorders. Researchers already realize that commonly occurring gene variants have only a modest role in the complex medical conditions with the most public health repercussions.

In this week’s paper, “Evolution and Functional Impact of Rare Coding Variations from Deep Sequencing of Exomes,” investigators described their study of the protein-coding sections of genomes from almost 2,440 individuals. The participants were 1,351 people of European extraction and 1,088 of African ancestry.

The study is a first step toward understanding how rare genetic variants contribute to some of the leading chronic illness causes of death in the world. It was conducted as part of the mission of the Seattle GO at the University of Washington and the Broad GO at Harvard University and MIT, both funded by the National Institute of Health’s National Heart Lung and Blood Institute Exome Sequencing Project. The exome consists of the protein-coding regions of the genome.

The overall project encompasses a great many individuals who have distinct traits, such as heart attacks before old age, strokes, or a high body mass index, to discover the genes and molecular mechanisms behind these conditions. Low cost, rapid sequencing of whole genomes is on its way to becoming clinically feasible. The information gleaned would be more useful if statistical and experimental methods could more accurately identify gene variations that regulate biological processes and produce functionally significant proteins. Such methods would link gene variations to disease causes and provide information for preventing and treating diseases.

The other senior author of the paper from the Exome Sequencing Project is Michael J. Bamshad, University of Washington professor of pediatrics in the Division of Genetic Medicine. Researchers from eight institutions across the nation collaborated.

The group sequenced and compared 15,585 human protein-coding genes. They located more than a half-million single-letter DNA code variations in their sample populations. The majority of these variations arose recently in human evolutionary history and so were rare, novel, and specific either to the African or the European study populations, the researchers discovered.

The researchers went on to pick just those single-letter variations in the DNA that might affect the functions of proteins. Alterations in protein functions are among the key ways genetic differences spin into disease traits. They estimated that a little more than 2 percent of the approximately 13,600 single nucleotide variations each person carried, on average, influenced the function of about 313 genes per genome. More than 95 percent of the single-letter code changes predicted to be functionally important were rare in the overall study population.

How did so many rare variations affecting protein function arise in the human genetic code? The researchers suggest that this excess of rare variations is due to a combination of demographic and evolutionary forces. Both European and African populations grew exponentially beginning around 10,000 years ago, but in the past 5,000 years growth rates accelerated leading to the billions of people living today.

The dramatic recent increase in population size has therefore profoundly influenced the spectrum of protein-coding variation present in humans. The scientists calculated the mean average of novel, single-letter code variations in their study subjects: 549 per individual overall. People of African descent had about twice the number of new variations compared to those of European descent, or 762 versus 382.

The researchers measured the effects of natural selection on rare coding variation. To do so, they also brought in genetic details from genes highly specific to humans relative to chimps and macaques to look for what are called “selective sweeps.” A selective sweep occurs when natural selection increases the frequency of a beneficial variant in a population. The beneficial variant doesn’t travel alone. Nearby genetic material is swept along with it. Included among the genes the scientists culled out as affected by positive selection were those related to the sense of smell and to the use of energy.

The researchers also learned that most of the protein-coding variations identified in their study were predicted to be harmful. Rare variation contributes not simply to each individual’s uniqueness, but also to the  risk for life-shortening illnesses.

What are the implications of these findings for understanding disease and advancing personalized medicine? Before answering, the researchers pointed to present limitations in robustly identifying functional important gene variation.

“Nevertheless,” they said, “there was considerable rare genetic variation among individuals that is predicted to be functional, which could explain variability in disease risk and in drug response.” The researchers would like more powerful tests to detect the effects of rare genetic variations on human health. They suggest that accounting gene-by-gene might improve research methods. They added that the population-specific nature of most of the single-letter code changes will make it challenging to replicate disease associations with a variant across the world’s people.

In addition to Akey and Bamshad, other researchers on the study were Jacob A. Tennessen, Timothy D. O’Connor, Wenqing Fu, Sean McGee, Mark J. Rieder, and Deborah A. Nickerson, all of the UW Department of Genome Sciences; Abigail W. Bigham of the UW Department of Pediatrics; Eimear E. Kenny, Simon Gravel and Carols D. Bustamante of Stanford University; Ron Do Stacey Gabriel, David Altshuler, and Shamil Sunyaev of the Broad Institute of MIT and Harvard University; Xiaoming Liu and Eric Boerwinkle , of the Texas Health Sciences Center in Houston; Goo Jun, Hyun Min Kang and Goncalo Abecasis of the University of Michigan; Daniel Jordan of the Division of Genetics at Brigham & Women’s Hospital in Boston; and Suzanne M. Leal of the Department of Molecular and Human Genetics at Baylor College of Medicine. The Center for Human Genetic Research at Massachusetts General Hospital and the Human Genome Sequencing Center at Baylor College of Medicine also contributed to this study.

The findings, published May 16 in the open-access online journal PLoS ONE, suggest that we unconsciously make gay and straight distinctions.

"It may be similar to how we don't have to think about whether someone is a man or a woman or black or white," said lead author Joshua Tabak, a psychology graduate student at the University of Washington. "This information confronts us in everyday life."

Vivian Zayas at Cornell University is the other author of the paper. Funding was provided by Cornell University and the National Science Foundation.

Tabak says that our ability to spontaneously assess sexual orientation based on observation or instinct conflicts with the assertion that if people just kept their sexual orientation to themselves then no one else would know and discrimination wouldn't exist, an argument frequently used by opponents of anti-discrimination policies for lesbian, gay and bisexual people.

Examples of faces used in the gaydar experiment.

Tabak JA, Zayas V (2012) The Roles of Featural and Configural Face Processing in Snap Judgments of Sexual Orientation. PLoS ONE 7(5): e36671.

In the study, 129 college students viewed 96 photos each of young adult men and women who identified themselves as gay or straight. Concerned that facial hair, glasses, makeup and piercings might provide easy clues, the researchers only used photos of people who did not have such embellishments. They cropped the grayscale photos so that only faces, not hairstyles, were visible.

For women's faces, participants were 65 percent accurate in telling the difference between gay and straight faces when the photos flashed on a computer screen. Even when the faces were flipped upside down, participants were 61 percent accurate in telling the two apart.

At 57 percent accuracy, they had a harder time differentiating gay men from straight men. The participants' accuracy slipped to 53 percent – still statistically above chance – when the men's faces appeared upside down.

The difference in accuracy for men’s and women’s faces was driven by more false alarm errors with men’s faces – that is, a higher rate of mistaking straight men’s faces as gay.

This may be because participants are more familiar with the concept of gay men than with lesbians, so they may have been more liberal in judging men's faces as gay, Tabak suspects. Another possibility is that the difference between gay and straight women is simply more noticeable than the difference between gay and straight men, Tabak said.

He was surprised that participants were above-chance judging sexual orientation based on upside down photos flashed for just 50 milliseconds, about a third the time of an eyeblink.

Don't think you have gaydar? You're not alone. Tabak says that in his experiments there are "always a small number of people with no ability to distinguish gay and straight faces."

It's unclear why some have better gaydar than others, since studies have only tested this aptitude in college students. Tabak speculates that "people from older generations or different cultures who may not have grown up knowing they were interacting with gay people" may be less accurate in making gay versus straight judgments.

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For more information, contact Tabak at 415-787-0009 or tabak@uw.edu.

Treatments were administered through an innovative device that quickly delivered the insulin to the brain. No side-effects were reported. The results were announced today at the Alzheimer’s Disease Research Summit 2012: Path to Treatment and Prevention taking place at the National Institutes of Health in Bethesda, Md.

Craft reported that growing evidence points to insulin playing a vital role in brain function, with decreased levels possibly contributing to memory problems, atrophy and other Alzheimer’s-related brain changes. She said scientists believe that normalizing brain insulin levels might be beneficial in treating the disease.

An image of the brain from the Alzheimer's Disease Research Summit 2012 banner

A new, larger study is planned that will recruit 240 volunteers for a year-long treatment trial at multiple sites across the U.S. Study participants with mild cognitive impairment or mild Alzheimer’s dementia will receive insulin treatment or a placebo.

At the end of one year, researchers will compare cognition, memory and functional performance between the two groups. Additionally, biomarkers associated with Alzheimer’s disease (levels of tau and amyloid proteins) will be measured in cerebrospinal fluid, and Alzheimer’s associated brain atrophy will be measured through brain imaging. At the end of the study year, all participants will receive the nasal insulin spray for 6 months.

The trial will be conducted in collaboration with the Alzheimer’s Disease Cooperative Study Consortium, a National Institute on Aging-supported network of academic medical centers and clinics experienced in designing and conducting Alzheimer’s clinical trials.

“This study allows more definitive testing of a promising treatment for Alzheimer’s disease,” said Laurie Ryan, program director of Alzheimer’s Clinical Trials at the National Institute on Aging at NIH, the lead institute studying age-related cognitive decline. “This larger, more in-depth clinical trial of insulin nasal spray will be a significant step forward in understanding the safety and effectiveness of this approach.”

Craft was the lead author of a study published in the Archives of Neurology in September 2011 that found low doses of insulin delivered to the brain through nasal sprays helped improve memory in people with mild cognitive impairment and early Alzheimer's disease.

A push to find new treatments and preventions for Alzheimer's disease is the focus of this week’s Alzheimer’s Disease Research Summit, the largest-ever government-sponsored summit for the disease that has brought together nearly 600 researchers from around the world.

More than 5 million people in the US have Alzheimer's disease, and the numbers are expected to grow. This week's program is a result of plans established by the National Alzheimer's Project Act, signed into law by President Obama last year and expected to be finalized today at the summit. The top goal is to find a cure for Alzheimer’s Disease by 2025.

The certificates, available to undergraduates, cover business essentials, database management and business localization for the international marketplace. Students can use the programs to explore new types of work they want to pursue after graduating, or learn more about how to apply the skills they acquire from their current degree programs to real careers.

“The certificates can help students test out or delve into a topic,” said Mary Larson, program management director for UW Educational Outreach.

The courses are taught by industry professionals who offer real-world perspectives on targeted careers. For instance, each of the three instructors who will teach the Certificate in Localization has over a decade of experience doing localization and project management for global companies including Microsoft and Siemens.

The Certificate in Business Essentials prepares students for work at most any kind of organization by teaching them practical skills in marketing, management and finance. As part of the program, students will write a business plan for a startup, product or existing organization.

“Don’t be afraid of the word ‘business’ in the title,” Larson said. Even students who have never had an interest in taking business classes will find it valuable, she said. That’s because any kind of employer—a nonprofit, a business or a government—will have marketing, management and finance functions. The courses teach students the concepts behind those functions as well as practical skills.

Students who enroll in the Certificate in Database Management program will learn the fundamentals of database management technology, design, development and administration. The certificate is applicable to students in a wide range of degree programs since so many different kinds of businesses collect vast amounts of data. “Banks, airlines, Internet companies—they’re all about data and it has to be managed,” Larson said.

Instructors of regular degree classes might know students who can benefit from the certificate courses.

“A German language professor might tell a student: ‘Don’t take my word that your language is valuable. Hear from the professionals teaching the localization certificate about how vital it is to multinational companies that are making giant investments in global markets,’” said Larson.

In addition to learning valuable skills, students will be more marketable to prospective employees. A student with a resume that includes a degree as well as a specialized certificate will be more attractive to an employer, Larson said.

“A certificate from UW is always valuable in this region,” Larson said. “We know that from many years of offering certificates.”

Participants earn nine or more credits over the nine week summer period and pay regular summer tuition.

Interested students are welcome to attend information sessions with the instructors. The business essentials information session is May 23 at 6 p.m. at Savery Hall, room 137. The database management instructor will meet prospective students May 23 at 4 p.m. and May 29 at 6 p.m.  in MGH 420. Students are invited to hear more about the localization program May 30 at 6 p.m. in Denny Hall, room 308.

For the past decade scientists have outlined new areas suitable for mammals likely to be displaced as climate change first makes their current habitat inhospitable, then unlivable. For the first time a new study considers whether mammals will actually be able to move to those new areas before they are overrun by climate change. Carrie Schloss, University of Washington research analyst in environmental and forest sciences, is lead author of the paper out online the week of May 14 in the Proceedings of the National Academy of Sciences.

"We underestimate the vulnerability of mammals to climate change when we look at projections of areas with suitable climate but we don't also include the ability of mammals to move, or disperse, to the new areas," Schloss said.

The percentage of mammal species unable to keep pace with climate change in the Americas range from zero and low (blue) to a high of nearly 40 percent (light orange).

U of Washington

Indeed, more than half of the species scientists have in the past projected could expand their ranges in the face of climate change will, instead, see their ranges contract because the animals won't be able to expand into new areas fast enough, said co-author Joshua Lawler, UW associate professor of environmental and forest sciences.

In particular, many of the hemisphere's species of primates – including tamarins, spider monkeys, marmosets and howler monkeys, some of which are already considered threatened or endangered – will be hard-pressed to outpace climate change, as are the group of species that includes shrews and moles. Winners of the climate change race are likely to come from carnivores like coyotes and wolves, the group that includes deer and caribou, and one that includes armadillos and anteaters.

The analysis looked at 493 mammals in the Western Hemisphere ranging from a moose that weighs 1,800 pounds to a shrew that weighs less than a dime. Only climate change was considered and not other factors that cause animals to disperse, such as competition from other species.

To determine how quickly species must move to new ranges to outpace climate change, UW researchers used previous work by Lawler that reveals areas with climates needed by each species, along with how fast climate change might occur based on 10 global climate models and a mid-high greenhouse gas emission scenario developed by the U.N. Intergovernmental Panel on Climate Change.

The UW researchers coupled how swiftly a species is able to disperse across the landscape with how often its members make such a move. In this case, the scientists assumed animals dispersed once a generation.

While bison cross this highway, they and other mammals may be less able to traverse or go around human-dominated landscapes, such as cities, found in the path the animals are taking to territory with climate that suits them.

C Schloss/U of Washington

It's understandable, for example, that a mouse might not get too far because of its size. But if there are many generations born each a year, then that mouse is on the move regularly compared to a mammal that stays several years with its parents in one place before being old enough to reproduce and strike out for new territory.

Western Hemisphere primates, for example, take several years before they are sexually mature. That contributes to their low-dispersal rate and is one reason they look especially vulnerable to climate change, Schloss said. Another reason is that the territory with suitable climate is expected to shrink and to reach the new areas animals in the tropics must generally go farther than in mountainous regions, where animals can more quickly move to a different elevation and a climate that suits them.

Those factors mean that nearly all the hemisphere's primates will experience severe reductions in their ranges, Schloss said, on average about 75 percent. At the same time species with high dispersal rates that face slower-paced climate change are expected to expand their ranges.

"Our figures are a fairly conservative – even optimistic – view of what could happen because our approach assumes that animals always go in the direction needed to avoid climate change and at the maximum rate possible for them," Lawler said.

The researchers were also conservative, he said, in taking into account human-made obstacles such as cities and crop lands that animals encounter. For the overall analysis they used a previously developed formula of "average human influence" that highlights regions where animals are likely to encounter intense human development. It doesn't take into account transit time if animals must go completely around human-dominated landscapes.

"I think it's important to point out that in the past when climates have changed – between glacial and interglacial periods when species ranges contracted and expanded – the landscape wasn't covered with agricultural fields, four-lane highways and parking lots, so species could move much more freely across the landscape," Lawler said.

Carrie Schloss

U of Washington

"Conservation planners could help some species keep pace with climate change by focusing on connectivity – on linking together areas that could serve as pathways to new territories, particularly where animals will encounter human-land development," Schloss said. "For species unable to keep pace, reducing non-climate-related stressors could help make populations more resilient, but ultimately reducing emissions, and therefore reducing the pace of climate change, may be the only certain method to make sure species are able to keep pace with climate change."

The third co-author of the paper is Tristan Nuñez, now at University of California, Berkeley. Both Schloss and Nuñez worked with Lawler while earning their master's degrees. Lawler did this work with support from the UW School of Environmental and Forest Sciences using, in part, models he previously developed with funding from the Nature Conservancy and the Cedar Tree Foundation.

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For more information:
Schloss, cell 440-666-6389, cschloss@uw.edu
Lawler, 206-685-4367, jlawler@u.washington.edu (Note: Lawler is away from the office the week of May 14 but will check for messages once or twice a day)

Drops of red and blue liquid move along the upper and lower surface of the vibrating UW platform at speeds up to 1 inch per second. This combined image shows drops as they move toward the center and merge.

Karl Bohringer, UW

"This allows us to move drops as far as we want, and in any kind of layout that we want," said Karl Böhringer, a UW professor of electrical engineering and bioengineering. The low-cost system, published in a recent issue of the journal Advanced Materials, would require very little energy and avoids possible contamination by diluting or electrifying the samples in order to move them.

The simple technology is a textured surface that tends to push drops along a given path. It's inspired by the lotus effect – a phenomenon in which a lotus leaf's almost fractal texture makes it appear to repel drops of water.

"The lotus leaf has a very rough surface, in which each big bump has a smaller bump on it," Böhringer said. "We can't make our surface exactly the same as a lotus leaf, but what we did is extract the essence of why it works."

A drop of liquid sits on the textured silicon surface that has arced rungs to guide the drop, and a grid of pillars to keep the drop in the channel.

Karl Bohringer, UW

Researchers used an audio speaker or machine to vibrate the platform at 50 to 80 times per second.  The asymmetrical surface moves individual drops along predetermined paths to mix, modify or measure their contents. Changing the vibration frequency can alter a drop's speed, or can target a drop of a certain size or weight.

"All you need is a vibration, and making these surfaces is very easy. You can make it out of a piece of plastic," Böhringer said. "I could imagine this as a device that costs less than a dollar – maybe much less than that – and is used with saliva or blood or water samples."

A close-up of the UW surface showing the arc edges and adjacent pillars.

Karl Bohringer, UW

The type of system is known as a "lab in a drop": all the ingredients are inside the drop, and surface tension acts as the container to keep everything together.

A student tried using a smartphone's speaker to vibrate the platform, but so far a phone does not supply enough energy to move the drops. To better accommodate low-energy audio waves, the group will use the UW's electron beam lithography machine to build a surface with posts up to 100 times smaller.

"There’s good evidence, from what we’ve done so far, that if we make everything smaller then we will need less energy to achieve the same effect," Böhringer said. "We envision a device that you plug into your phone, it’s powered by the battery of the phone, an app generates the right type of audio vibrations, and you run your experiment."

Co-authors of the paper are former UW undergraduate Todd Duncombe and former UW graduate student Yegȃn Erdem, both at the University of California, Berkeley; former UW postdoctoral researcher Ashutosh Shastry, now at Corium International in Menlo Park, Calif.; and Rajashree Baskaran, a UW affiliate assistant professor of electrical engineering who works at Intel Corp.

The research was funded by the National Science Foundation, the National Institutes of Health, Intel and the UW's Technology Gap Innovation Fund.

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For more information, contact Böhringer at 206-221-5177 or karl@ee.washington.edu.

Sean Dreilinger / Flicker Creative Commons

Washington's housing market in the first quarter of 2012 saw the highest seasonally adjusted sales since the first-time buyer tax credit program expired in 2010, according to the Runstad Center for Real Estate Studies at the University of Washington.

Overall, sales returned to a level close to the average of the last 20 years, reflecting both a return to the market by first-time and move-up buyers and continued interest in distressed properties by investors.

“The prevalence of distressed properties in some neighborhoods held prices back,” said Glenn Crellin, associate director for research at the center. In areas with more desirable properties, he said, prices are up because fewer distressed properties are holding the market back. "It is clear some markets are seeing increasing prices as the available inventory of quality properties has dwindled significantly."

The seasonally adjusted sales rate during the quarter was 97,000 homes, meaning that if the sales rate for the quarter continued for a year, that number of homes would be sold. That rate is 7.9 percent above the last quarter of 2011 and 11.3 percent higher than a year ago.

"Despite the stronger market, median home prices continued to decline compared to a year earlier," Crellin said. The first quarter median fell to $208,300, a decline of 8.7 percent from the same period in 2011. Crellin said the drop in the median price does not mean that prices of individual homes are uniformly continuing to decline. Rather, falling prices are primarily in neighborhoods with a significant number of homes at some stage of foreclosure. Nine counties reported higher median prices.

Sales, median home prices and affordability data for each of Washington’s 39 counties are available at the Runstad website.

The combination of lower median prices and low mortgage interest rates means the affordability of homes has not been higher in the last 20 years.  According to the center’s Housing Affordability Index, the median-income family in the state had 84.7 percent more income than the minimum required to buy a median-price home, assuming a 20 percent down payment. The data show that in all 39 counties in the state, a median-income family could afford a median-priced home.

“Affordability is also at a record high for first-time buyers, and rent increases are encouraging them to begin seriously pursuing home ownership,” said Faye Nelson, president of Washington Realtors.

In Washington’s urban counties, the greatest quarterly gain in sales was 33 percent in Chelan County, while the greatest decline, 7.1 percent, happened in Whatcom County. The only year-to-year slowing of sales was a 0.6 percent decline in Benton/Franklin counties.

Among the urban markets, median home prices ranged from a high of $322,400 in King County to a low of $128,000 in Asotin County.

“The shadow inventory of distressed properties continues to hold back the market in some neighborhoods,” Crellin said, “but other neighborhoods have a real shortage of homes on the market, leading to increasing prices, short marketing times and often multiple offer situations. It is truly a story of two markets.”

The Runstad Center produces home sales statistics in partnership with Washington Realtors. Each quarterly release coincides with information from the National Association of Realtors regarding median home prices by metropolitan area.

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For more information, contact Crellin at 206-685-8020 or crellin@uw.edu.

The University of Washington,  the University of Texas Medical Branch at Galveston and a Seattle biotech company, Kineta Inc., announced receipt of the funding May 8.

Ebola virions

The grant to advance next generation antiviral therapeutics is from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

“This award enables us to push further and work with more high priority viruses,” said  Dr. Michael Gale, Jr., UW professor of immunology and principal investigator of the grant.  “These diseases are major concerns of the United States government for their risk of sparking a pandemic and their potential use as bioterrorist weapons.  By utilizing an innate immune pathway we hope to develop better drugs that won’t be out-smarted by viral mutation.”

Gale, who is also an  adjunct professor of global health and microbiology and affiliate investigator of the Clinical Research Division of the Fred Hutchinson Cancer Research Center, directs the NIH-supported Center for The Study of Immune Mechanisms of Virus Control  at UW.  He studies innate immunity to virus infection, and the intracellular immune processes and virus-host interactions that control viral replication and infection outcome.

Nipah virions isolated from spinal fluid.

CDC

“A primary mission of the Galveston National Lab is to engage our unique resources in translating research ideas into products aimed at combating emerging infectious diseases,” said Geisbert. “This collaboration between Kineta, the UW and the GNL leverages expertise and resources from academia and industry to promote the advancement of countermeasures against two high-priority public health and biodefense threat agents.”

“The potential human benefit is great, with these therapies holding potential to treat an array of common and obscure viruses, those of moderate and grave concern,” said Iadonato.

This infusion of support will help Kineta move two, small molecule drug candidates closer to  human clinical trials. The program, Agonists of the Retinoic Acid Inducible Gene I Innate Immune Pathway,  is geared toward infectious diseases in need of better treatments:  influenza, hepatitis C, West Nile virus, and respiratory syncytial virus.  Retinoic Acid Inducible Gene I is a molecular "on/off" switch that triggers the human body's innate immune system to eliminate infection.

This grant will increase the number of disease targets to include less commonly known henipaviruses and filoviruses such as yellow fever, Ebola, Marburg, plague and others. Currently, treatment of all viral diseases is severely limited by a lack of effective drugs.