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Video game improves balance in youth with autism  external link

Photo: Child posing on balance board

Brittany Travers, an investigator at the UW–Madison Waisman Center, works with a study participant playing a video game designed to help youth with autism improve their balance. Difficulties with balance are commonly thought to relate to more severe autism spectrum disorder symptoms and impaired activities in daily living. Photo: Andy Manis

Playing a video game that rewards participants for holding various “ninja” poses could help children and youth with autism spectrum disorder (ASD) improve their balance, according to a recent study in the Journal of Autism and Developmental Disorders led by researchers at the University of Wisconsin-Madison.

Balance challenges are more common among people with ASD compared to the broader population, says study lead author Brittany Travers, and difficulties with balance and postural stability are commonly thought to relate to more severe ASD symptoms and impaired activities in daily living.

“We think this video game-based training could be a unique way to help individuals with ASD who have challenges with their balance address these issues,” says Travers, an investigator at UW–Madison’s Waisman Center and an assistant professor of kinesiology.

In this pilot study — the largest ever to look at the effects of balance training on individuals with ASD — 29 participants between the ages of 7 and 17 with ASD completed a six-week training program playing a video game developed by the researchers.

Photo: Brittany Travers

Brittany Travers

By the end of the program, study participants showed significant improvements in not only their in-game poses but also their balance and posture outside of the game environment.

According to Travers, balance improvements outside the video game context are especially important. “Our participants are incredibly clever when it comes to finding ways to beat video games!” she says. “We wanted to make sure that the improvements we were seeing were truly balance-related and not limited to the video game.”

Ten out of 11 study participants who completed a post-game questionnaire also said they enjoyed playing the video games.

“We always aim to make the interventions fun,” says Travers. “We have couched a rigorous exercise (by the end of some gaming sessions, participants had been standing on one foot for 30 minutes) in a video game format, so we were delighted to hear that the participants enjoyed the game.”

Travers developed the video game with help from Andrea Mason, professor of kinesiology at UW-Madison, Leigh Ann Mrotek, professor of kinesiology at UW-Oshkosh and Anthony Ellertson, program director of gaming and interactive technology at Boise State University.

The gaming system uses a Microsoft Kinect camera and a Nintendo Wii balance board connected to software developed on a Windows platform using Adobe Air.

“Players see themselves on the screen doing different ‘ninja’ poses and postures, and they are rewarded for doing those poses and postures; that’s how they advance in the game,” says Travers.

“We always aim to make the interventions fun … so we were delighted to hear that the participants enjoyed the game.”

Brittany Travers

The study also explored individual differences that might predict who would benefit most from this type of video game-based balance training.

For example, the study showed that participants with some characteristics, such as ritualistic behaviors (like the need to follow a set routine around mealtimes or bedtime) did not benefit as much from the video game as those without these behaviors.

On the other hand, some characteristics, such as body mass index or IQ, did not influence whether a participant benefited from balance training.

“There is a lot of variability in the clinical profile of ASD, and it’s unlikely that there will be a one-size-fits-all approach for balance training that helps all individuals with ASD,” says Travers.

Researchers are working to make the game more accessible to different individuals within the autism spectrum. “We already have some features that help — the game has very little verbal instruction, which should make it more accessible to individuals who are minimally verbal,” says Travers. “Ultimately, we would like to move this video game-based training outside the lab.”

This work was supported by the Brain and Behavior Research Foundation’s NARSAD Young Investigator Grant, the Hartwell Foundation’s Individual Biomedical Research Award, the University of Wisconsin System’s WiSys Technology Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30 HD003352, U54 HD090256 and T32 HD007489].++

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In the heart of devastating outbreak, research team unlocks secrets of Ebola  external link

In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in Cell Host & Microbe, a scientific team led by the University of Wisconsin–Madison has identified signatures of Ebola virus disease that may aid in future treatment efforts.

Conducting a sweeping analysis of everything from enzymes to lipids to immune-system-associated molecules, the team — which includes researchers from Pacific Northwest National Laboratory (PNNL), Icahn School of Medicine at Mount Sinai, the University of Tokyo and the University of Sierra Leone — found 11 biomarkers that distinguish fatal infections from nonfatal ones and two that, when screened for early symptom onset, accurately predict which patients are likely to die.

Photo: Gloved hand holding empty vial

A vial is labeled and prepared to hold blood from an Ebola patient in Sierra Leone. All photos courtesy of Kawaoka Lab

With these results, says senior author Yoshihiro Kawaoka, a virology professor at the UW–Madison School of Veterinary Medicine, clinicians can prioritize the scarce treatment resources available and provide care to the sickest patients.

Studying Ebola in animal models is difficult; in humans, next to impossible. Yet, in Sierra Leone in 2014, a natural and devastating experiment played out. In September of that year, an Ebola outbreak like no other was beginning to surge in the West African nation. By December, as many as 400 Ebola cases would be reported there each week.

That fall, Kawaoka sought access to patient samples. He has spent a career trying to understand infectious diseases like Ebola — how do they make people sick, how do bodies respond to infection, how can public health officials stay at least a step ahead?

“Here, there is a major outbreak of Ebola. It is very rare for us to encounter that situation,” says Kawaoka, who is also a professor of virology at the University of Tokyo.

Photo: Health workers in safety suits

Health workers tend to a patient at one of Sierra Leone’s military hospitals, where many of the country’s 8,000 Ebola patients have received treatment since an outbreak began in West Africa in December 2013.

Yet blood samples were proving difficult to obtain and people continued to die.

Then, just weeks before Christmas, Kawaoka learned about a colleague in his very own department at UW–Madison, a research fellow from Sierra Leone named Alhaji N’jai, who was producing radio stories for people back home to help them protect themselves from Ebola. The pair forged a fortuitous partnership.

“He knows many people high up in the Sierra Leone government,” says Kawaoka. “He is very smart and very good at explaining things in lay terms.”

By Christmas, Kawaoka, N’jai and Peter Halfmann, a senior member of Kawaoka’s team, were in Sierra Leone.

“On the first trip, Alhaji took me to Parliament and we talked to a special advisor to the president, then the vice chancellor of the University of Sierra Leone,” says Kawaoka. “We got the support of the university, which helped us identify military hospitals and provided space. We went to the Ministry of Health and Sanitation and the chief medical officer and we explained what we hoped to do.”

Photo: Kawaoka with Edundayo Thompson

Kawaoka meets with Ekundayo Thompson, vice chancellor of the University of Sierra Leone, while in the African nation to establish a partnership to study and fight Ebola while improving the research capacity and infrastructure of the university.

By February of 2015, Kawaoka and other select senior researchers on his  team, including Amie Eisfeld, set up a lab in a military hospital responding to the outbreak in the capital city of Freetown (the researchers never entered patient wards). With the approval of patients and the government of Sierra Leone, health workers collected blood samples from patients after they were diagnosed with Ebola and at multiple points thereafter.

They obtained 29 blood samples from 11 patients who ultimately survived and nine blood samples from nine patients who died from the virus. The samples were transported to the lab where Kawaoka’s experienced and expertly trained team inactivated the virus according to approved protocols. Blood samples were subsequently shipped to UW–Madison and partner institutions for analysis.

For comparison, the research team also obtained blood samples from 10 healthy volunteers with no exposure to Ebola virus.

SIDEBAR: Video reaches ‘Spiderman’ audience with Ebola messaging

“Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins and other molecules to identify those of most interest,” says Katrina Waters, a biologist at PNNL and a corresponding author of the study. “This may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus.”

The team found that survivors had higher levels of some immune-related molecules, and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in processes like blood coagulation, and more pronounced activation of some types of immune cells.

Photo: Team standing in front of military hospital

UW-Madison’s Yoshihiro Kawaoka, Peter Halfmann and Alhaji Njai stand outside of a military hospital with Foday Sahr, a Sierra Leone military official and chair of microbiology at the University of Sierra Leone.

Pancreatic enzymes also leaked into the blood of patients who died, suggesting that damage from these enzymes contributes to the tissue damage characteristic of fatal Ebola virus disease.

And, critically, the study showed that levels of two biomarkers, known as L-threonine (an amino acid) and vitamin D binding protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.

“We want to understand why those two compounds are discriminating factors,” says Kawaoka. “We might be able to develop drugs.”

When Ebola virus leads to death, experts believe it is because of overwhelming viral replication. Symptoms of infection include severe hemorrhaging, vomiting and diarrhea, fever and more.

Kawaoka and his collaborators hope to better understand why there are differences in how patients’ bodies respond to infection, and why some people die while others live. The current study is part of a larger, multicenter effort funded by the National Institutes of Health.

“This may be the most thorough analysis yet of blood samples of patients infected with the Ebola virus.”

Katrina Waters

“The whole purpose is to study the responses of human and animal bodies to infection from influenza, Ebola, SARS and MERS, and to understand how they occur,” Kawaoka explains. “Among the various pathways, is there anything in common?”

In the current Ebola study, the team found that many of the molecular signals present in the blood of sick, infected patients overlap with sepsis, a condition in which the body — in response to infection by bacteria or other pathogens — mounts a damaging inflammatory reaction.

And the results contribute a wealth of information for other scientists aimed at studying Ebola, the study authors say.

Kawaoka says he is grateful to UW–Madison, University Health Services and Public Health Madison and Dane County for assistance, particularly with respect to his research team’s travel between Madison and Sierra Leone. Each provided protocols, monitoring, approval and other needed support during the course of the study.

“I hope another outbreak like this never occurs,” says Kawaoka. “But hopefully this rare opportunity to study Ebola virus in humans leads to fewer lives lost in the future.”

The study was funded by a Japanese Health and Labor Sciences Research Grant; by grants for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by Emerging/Re-emerging Infectious Diseases Project of Japan; and by an administrative supplement to grant U19AI106772, provided by the U.S. National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Support was also provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai and by a grant from the National Institute of General Medical Sciences (P41 BM013493). Some analyses were performed at the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the U.S. Department of Energy Office of Biological and Environmental Research.

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Images of strange solar system visitor peel away some of the mystery  external link

A strange visitor, either asteroid or comet, zipping through our solar system at a high rate of speed is giving astronomers a once-in-a-generation opportunity to examine up close an object from somewhere else in our galaxy.

Video: GIF of moving comet or asteriod as seen from telescope

Images of an interloper from beyond the solar system — an asteroid or a comet — were captured on Oct. 27 by the 3.5-meter WIYN Telescope on Kitt Peak, Ariz. WIYN Observatory/Ralf Kotulla

“It’s a really rare object,” explains Ralf Kotulla, a University of Wisconsin-Madison astronomer who, with colleagues from UCLA and the National Optical Astronomy Observatory (NOAO), used the 3.5 meter WIYN Telescope on Kitt Peak, Arizona, to take some of the first pictures of the solar system interloper.

The object, known to astronomers as 1I/2017 U1, measures 180 meters by 30 meters. In shape, the object resembles a fat cigar, half a city block long, and was first discovered Oct. 19 by astronomers at the University of Hawaii combing the sky for near-Earth objects. Since then, astronomers who have access to telescope time have been zooming in on the object to see what they might learn.

According to Kotulla, the interloper is speeding through the solar system at an astonishing 40,000 miles per hour. The high rate of speed and the orbit of the object could not be explained in the context of more run-of-the-mill comets or asteroids in our solar system.

Graphic: Diagram of object moving through solar system

This animation shows the path of the asteroid — or perhaps a comet — as it passed through our inner solar system in September and October 2017. From analysis of its motion, scientists calculate that it probably originated from outside of our solar system. NASA/JPL-Caltech

1I/2017 U1 dropped into our solar system from “above” the ecliptic, the plane where most planets and asteroids orbit the sun, and is now skipping away from the solar system, headed back to interstellar space.

“This object has considerable speed. It is not bound to the sun” like comets or asteroids native to our solar system, Kotulla explains. “Its orbit doesn’t take it anywhere near the major planets.”

The WIYN Telescope made its observations of 1I/2017 U1 on Oct. 27 shortly after the object’s closest pass to Earth. The WIYN team’s findings are reported online this week (Nov. 13, 2017) in a preprint on Astro-Ph. The gist of the report is that 1I/2017 U1 — aside from its origin beyond the solar system, its unusual orbit and shape, and high rate of speed — is unremarkable when its physical properties are compared to similar objects from our own solar system.

Photo: WIYN telescope building exterior

The WIYN telescope building against a sunset sky, with interior light on the telescope. Mark Hanna/NOAO/AURA/NSF

Because it is so small and moving at such a high rate of speed, the object, even to a relatively large telescope like WIYN, appears faint, a fuzzy spot on a background of stars. The combination of being faint and fast means that 1I/2017 U1 is unlikely to be observed by amateur astronomers, the cadre of sky watchers that typically identifies new comets or asteroids sweeping close to Earth.

From the WIYN observations, no coma — a nebulous envelope of dust and gas created when comets heat up as they pass near the sun — is apparent. The WIYN team also failed to see a tail, the signature feature of a comet.

Photo: Ralf Kotulla

Ralf Kotulla

But the absence of the fuzzy halo and a detectable tail, notes Kotulla, does not mean that it isn’t a comet.

“That’s one of the questions we’re trying to answer,” says the Wisconsin astronomer. “Comet or asteroid?”

The WIYN observations revealed that the object is elongated in shape and rotates on an axis about once every eight hours. From the perspective of Earth, the object is seen sideways and, as it spins on its axis, end-on, explaining variations in brightness as sunlight is reflected off the comet or asteroid. It also has a reddish tinge and a low albedo, suggesting 1I/2017 U1 lacks the coating of ice that many comets acquire as they spend most of their time in cold storage in the outer reaches of the solar system.

The upshot of the WIYN observations, says Kotulla, is that the visitor from some distant planetary system, beyond its robusto-cigar shape, looks very much like the objects that populate our own solar system.

Did you ever wonder how NASA spots asteroids that maybe getting too close to Earth for comfort? Watch and learn.

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UW entrepreneurial pipeline lands Lactic Solutions in biofuels marketplace  external link

When Jim Steele thinks back over the last seven years, from the early research on biofuels, followed by a dream of moving Lactic Solutions LLC technology to the marketplace, and now the acquisition of the company by Lallemand Biofuels & Distilled Spirits (a unit of Lallemand Inc.) last month, he is thankful for the network of UW-Madison entrepreneurial experts.

“UW-Madison is unique, according to my colleagues at other universities,” says Steele, co-founder and CEO of Lactic Solutions and UW–Madison Winder-Bascom Professor of food science. “UW–Madison may be ahead of its peers in providing support to entrepreneurial faculty and staff. However, most faculty and staff, including us in the early years, are not aware of the resources available to them.”

Steele’s advice for anyone else at UW–Madison with an idea for a product or interested in commercializing a discovery, is to get plugged into the university’s entrepreneurship pipeline early and take advantage of the tools available for turning those ideas into commercially viable solutions.

Photo: Jim Steele and Busra Aktas in lab

Jim Steele, pictured in his lab with research assistant Busra Aktas in 2013, says anyone at UW–Madison who has an idea for a product or is interested in commercializing a discovery should get plugged into the university’s entrepreneurship pipeline early. Photo: Wolfgang Hoffmann

In Steele’s case, partners in the process for Lactic Solutions have included the Wisconsin Alumni Research Foundation’s Accelerator Program (AP), UW–Madison’s Discovery to Product (D2P) office, the Great Lakes Bioenergy Research Center (GLBRC), gBETA, UW–Madison’s Law and Entrepreneurship Clinic and the Business and Entrepreneurship Clinic.

Steele and Jeff Broadbent are the scientific leads at Lactic Solutions. Broadbent is the associate vice president for research and associate dean of graduate studies, and professor in the Department of Nutrition, Dietetics and Food Sciences, at Utah State University. Together, their research is based on understanding the basic physiology, genetics and ecology of lactic acid bacteria.

Lactic acid bacteria are common contaminants in ethanol fermentations, where they compete with the yeast for nutrients and reduce biofuel yields. Industry typically uses antibiotics to control these contaminants. Lactic Solutions products are engineered lactic acid bacteria that produce ethanol and inhibitors active on the contaminating bacteria. These new products are of value to fuel ethanol producers interested in higher ethanol production yields and reduced consumption of antibiotics.

Steele’s research was originally funded by the Great Lakes Bioenergy Research Center. The GLBRC is led by UW–Madison, with Michigan State University as a major partner, and is one of three bioenergy research centers established by the U.S. Department of Energy in 2007.

“We received funding from GLBRC and that was the beginning of the process. Because of GLBRC’s early support, we then received a five-year grant from the U.S. Department of Agriculture,” Steele says. “That gave us stable funding and we were able to develop the data to support our first patent application.”

Steele says it was serendipity that led him to call Beth Werner, senior intellectual property manager at the Wisconsin Alumni Research Foundation (WARF) on a Friday to discuss his patent idea. He said he was considering sending an abstract for publication on Monday but was having second thoughts.

Photo: Left-to-right, Jeff Broadbent, Jim Steele, Peggy Steele

Lactic Solutions scientific leads Jim Steele (center) and Jeff Broadbent brought Peggy Steele onboard to utilize her business skills based on 10 years of working in the field of industrial cultures used in consumer products. Photo courtesy of Peggy Steele

“I asked if we should bother to protect the concept and Beth said we should,” Steele recalls. “We worked on writing the patent over the weekend and that became the foundation of Lactic Solutions.”

The first of Steele and Broadbent’s two patent applications was pending when they were at a USDA meeting four years ago reporting on their research results.

“After the meeting Jeff and I were sitting at the bar talking to people about the ethanol industry when the problem that they faced with contaminating lactic acid bacteria came up,” Steele says. “It was clear to both of us immediately that was a great application for our technology.”

With that epiphany, Steele and Broadbent brought Steele’s wife, Peggy, on board. She brought business skills to the mix based on 10 years of business development experience working in the field of industrial cultures used in consumer products.

“We met with ethanol producers and discovered that there really was a need in the market for what Lactic Solutions could offer,” Peggy Steele says. “It all came together — we had the right people involved, too.”

Steele credits Mark Cook, a UW–Madison animal sciences professor, for introducing them to D2P.

“Mark told me about the potential pitfalls, was a real caring person and an advocate for entrepreneurship on campus,” Steele recalls.

Cook, who died in September from complications related to cancer, helped establish D2P and was a prolific researcher and entrepreneur with more than 40 patents and three startup companies in the areas of health and agriculture.

Lactic Solutions joined D2P’s June 2015 Igniter program and spent the summer working with D2P staff and plowing through financials, a marketing plan and business opportunities. With D2P, the Steeles began to understand the industry better, connected with people who work in the ethanol industry and developed their marketing message.

“D2P helped us sharpen our strategy and put it into action,” Jim Steele says. “We were talking to potential customers the second day of the program. Those were critical conversations and really the whole summer with D2P was a major point of development for Lactic Solutions.”

“D2P filled gaps that we had, and was a great experience,” Peggy Steele says.

“I asked if we should bother to protect the concept and Beth said we should. We worked on writing the patent over the weekend and that became the foundation of Lactic Solutions.”

Jim Steele

While D2P helped Lactic Solutions hone its business appeal, technology development was supported by the WARF Accelerator Program, which selects WARF’s most commercially promising technologies and provides expert assistance and funding to enable achievement of commercially significant milestones. The AP also supplied two years of bridge funding, helping Lactic Solutions move from patent to prototype.

“On paper it all looked so easy,” Steele says. “Turns out it wasn’t so easy. That’s the way science goes.”

The AP also helped Steele meet potential collaborators in the industry.

“They taught me what the industry needs were and what simply would not work in industry. Also, the people at WARF were amazing all the way through the process. Mark Staudt and Rich Schifreen were true advocates from the beginning and their ability to connect us with the right programs was essential,” he says.

All those experiences led to a collaboration with gBETA, a community-based offshoot of gener8tor, a nationally renowned startup accelerator.

“With gBETA, we worked on communicating our message and generating items, like a logo, that are part of a professional image,” Steele says. “Communicating our message started in D2P but really got polished in gBETA.”

During gBETA’s program, companies meet with the gBETA cohort to refine their business model, strategize their growth, gain customer traction and pitch investors. Participants also learn about startup metrics and fundraising.

About the same time, partners in Lactic Solutions decided they needed a founder’s agreement and they sought the expertise of UW-Madison’s Law and Entrepreneurship Clinic. Simultaneously, they ended up working with the Business and Entrepreneurship Clinic on campus to build out the strategic plan.

Lactic Solutions is rare in that it did not need venture capital investors and was able to skip that step in the process of moving to the marketplace.

“In 2016, David Tenenbaum in UW Communications wrote a story about Lactic Solutions and that story got behind the firewall of the Renewable Fuels Association,” Steele says, referring to the leading trade association for America’s ethanol industry. “Suddenly all of these customers that we had been trying to contact started contacting us. And here we are — it doesn’t even seem that long ago that Jeff and I had our eureka moment while sitting and talking at a bar.”

“Go to D2P, go to WARF and go to gBETA. They are experts in their areas. There is a lot of help at the university that we became aware of as we were going through this process.”

Peggy Steele

The combination of WARF and UW-Madison resources has paid off for Lactic Solutions, as the startup company recently completed the cycle of innovation and ended up with several offers.

“We took the Lallemand offer because they had the best complimentary skills, motivation and interest to get the product to market,” Peggy Steele says.

If you feel that you have developed knowledge or technology that can add value, the Steeles recommend reaching out for help in commercialization, including patenting.

“Go to D2P, go to WARF and go to gBETA,” Peggy says. “They are experts in their areas. There is a lot of help at the university that we became aware of as we were going through this process. D2P was instrumental in helping us get all those dots connected.”

Jim Steele adds, “Most people cannot be an expert in every aspect of launching a business. The beauty of the UW system is that it provides access to the disciplines needed to make the whole thing work. Talking to people outside our areas of expertise played a key role in our success.”

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Molecular magnetism packs power with “messenger electron”  external link

Berry suggests that the new molecular magnet structure could be used in advanced computing, super-cold research, or further exploring the fundamentals of magnetism. David Tenenbaum

Electrons can be a persuasive bunch, or at least, a talkative bunch, according to new work from John Berry’s lab at the University of Wisconsin-Madison.

The spins of unpaired electrons are the root of permanent magnetism, and after 10 years of design and re-design, Berry’s lab has made a molecule that gains magnetic strength through an unusual way of controlling those spins.

Berry says the new structure that graduate student Jill Chipman created could lead to a breakthrough in quantam computing, an approach with such great potential that it could undermine today’s silicon-based supercomputers much as the telephone did the telegraph: A great leap forward that begins a slide into irrelevance.

The presence and activity, or “spin,” of unpaired electrons sets the strength of a permanent magnet, so molecules with a high degree of spin are a desirable target for chemists. The unusually large spin in the new magnetic molecule, Berry explains, results from a “messenger electron” that shuttles between an unpaired electron at each end of the rod-shaped molecule and persuades all three of them to adopt the same spin.

That agreement of spin, “orthogonality” in the jargon, adds strength to a permanent magnet.

Berry, a UW-Madison professor of chemistry, notes that in other materials, a traveling electron tends to oppose the spins of magnetic centers, reducing the magnetic strength. In Chipman’s new creation, however, the messenger electron is focused on harmony: like a traveling social worker, it causes the two remote unpaired electrons to take the same spin, adding strength and/or durability.

“Magnets are widespread in ultra-cold refrigeration, motors, computer hard drives and electronic circuits.”

John Berry

The new molecule, described in Chemistry – A European Journal, contains carbon, nickel, chlorine, nitrogen, and molybdenum, but lacks the costly rare earth elements that have bedeviled efforts to commercialize super-strong new magnets. Its structure suggests that the molecule could be formed into a polymer – a repeating chain of units like those found in plastics – raising the possibility of cheaper, stronger magnets.

“We tried to remove electrons from this molecule 10 years ago so it had an unpaired electron at each end, but did not get far,” Berry says. “We since learned that this made a chemical that is really temperature-sensitive, so Jill had to develop a low-temperature process that relies on dry ice to cool it to -78 degrees C.”

The “traveling social worker” electron establishes “a design principle that could be used to create many new magnetic molecules that behave as little bar magnets,” Berry says.

The discovery was also enabled by the arrival last summer an instrument called a SQUID magnetometer (Superconducting QUantam Interference Device) that can measure magnetism with great accuracy down to below 2 degrees above absolute zero.

Much of the focus of magnet innovation concerns greater strength, Berry says, “but there are all sorts of things people look for. We need both permanent magnets and those with ephemeral magnetization for different technical reasons. Magnets are widespread in ultra-cold refrigeration, motors, computer hard drives and electronic circuits.”

By going the next step, and miniaturizing magnets to a single molecule, that could enable quantam computing, Berry says. Quantam computing could be especially beneficial to chemists, who confront staggering complexity in trying to model the chemical reactions that are their bread and butter.

This work was supported in part by the National Science Foundation (CHE-1669994). Computational facilities were supported by the NSF under Grant CHE-0840494. The Bruker Impact™ II mass spectrometer was funded via a bequest from Paul J. and Margaret M. Bender.


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BuckySubmit helps with public access compliance at UW–Madison  external link

A new submission service is assisting researchers at the University of Wisconsin–Madison maintain compliance with the federal agencies that fund them. It is also helping researchers save time while providing public access to their manuscripts.

The service is called BuckySubmit and it works like this: A researcher goes to the website hosted by UW–Madison’s Ebling Library and follows the links to submit their manuscript once it has been accepted for publication. BuckySubmit staff review the manuscript to ensure it meets the federal funder’s requirements and then file it with the appropriate federal agencies.

Beginning with a National Institutes of Health (NIH) policy implemented nearly a decade ago, all 24 federal agencies that provide research funding now require published results be made available to the public through specific research repositories. The requirement is known as “public access” but maintaining compliance can be burdensome on researchers because each agency has its own rules and procedures.

About 2,800 researchers at UW–Madison are affected by the requirement.

“While the point of having rules in place to govern how funding is spent or how human subjects are treated is important from the perspective of protecting people or research investments, the volume of these mandates can often take time away from the research,” says Ryan Schryver, public access compliance specialist for Ebling Library.

Beginning with the NIH requirement, recently-retired former director of the Ebling Library for the Health Sciences, Julie Schneider, began building BuckySubmit with Schryver and Ebling Information Architecture Librarian Allan Barclay. The service launched in June 2017. The Office of the Vice Chancellor for Research and Graduate Education (OVCRGE) refers to it as Schneider’s “gift to campus.”

Today, Schryver oversees BuckySubmit, which represents a collaboration between OVCRGE and the School of Medicine and Public Health.

Years ago, Jean Phillips, director of the Schwerdtfeger Library at the UW–Madison Space Science and Engineering Center (SSEC), began analyzing publications from the center’s researchers. She compiled statistics on measures like internal and external collaborations, viewing it as one way to assess whether the institute was meeting its mission.

The National Oceanic and Atmospheric Administration, which funds SSEC’s Cooperative Institute for Meteorological Satellite Studies (CIMSS), recognized the value of this type of reporting so much so that these data, along with other metrics, are now ingrained in the CIMSS annual reporting process.

Today, Phillips also helps provide feedback to Schryver on the BuckySubmit architecture and worked with him to create a localized version of the service. She sees an extended benefit to BuckySubmit, beyond just easing the burdens of compliance: The repository could potentially offer a lens through which to study the research being conducted on campus.

Federal funders are interested in tracking publications data to show the reach and impact of taxpayer-funded research, Phillips says. “It is one way to get a handle on it.”

Additionally, researchers can use it to study trends and other emerging patterns in their publication data, as she and CIMSS Director and Associate Vice Chancellor for Research and Graduate Education, Steve Ackerman, did in 2009, publishing a paper on how they evaluated CIMSS’ performance using its publication records. It took several years of collecting and analyzing publications data for other purposes, Phillips says, but she and Ackerman have discussed doing a follow-up.

The data available through a research repository can help the university learn where articles are being published, how often students are co-authors, about emerging areas of research, about patterns in funding sources, whether institutional goals and educational missions are being met and more.

“You probably wouldn’t make critical decisions based on publications data alone, but it might be one valuable piece of information that sits alongside other sources,” says Phillips.

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New theory could open potent new applications for light  external link

One bar, two bars — it’s an all-too-common problem. You’re in a large building, driving in a remote area, or even right in the middle of a big city, but you can’t stream video, check email or even make a phone call — because your cellular signal is weak.

But the future may be different. University of Wisconsin–Madison electrical engineers have devised a new fundamental understanding that someday could lead to vast improvements in devices that gather or deliver information at any wavelength.

Photo: Cellular phone tower

UW–Madison electrical engineers have devised a new fundamental understanding that someday could lead to vast improvements in such things as the strength of cellphone signals. Pixabay

Led by Zongfu Yu, professor of electrical and computer engineering at UW–Madison, the researchers published details of their theory in the Nov. 9, 2017, issue of the journal Nature Communications.

Their research centers on a phenomenon known as electromagnetic scattering.

The electromagnetic spectrum includes everything from gamma rays, which have very short wavelengths, to the long wavelengths of radio waves. Visible light falls right in the middle. Every day, we interact with some aspect of the electromagnetic spectrum. For example, we see stars in the sky. We might have a dental X-ray, heat food in a microwave oven, or listen to news on an AM radio.

Each of these is a form of electromagnetic radiation — energy that travels and spreads, or radiates. When radiating energy, such as light, collides with any particle, the particle affects the direction the light travels. That’s known as scattering.

Photo: Zongfu Yu

Zongfu Yu

Conversely, a device’s cross section determines how much of that scattered electromagnetic radiation it can detect. For example, your phone’s antenna dictates what mobile signals it can detect.

“There’s a fundamental law that governs the scattering strengths and its relation to wavelengths,” says Yu. “That’s why we see the blue sky, that’s why we see the red sunset, and that’s why our cell phone antenna is a certain size and we can’t make it smaller.”

In their research, Yu and his collaborators demonstrated an approach to enhance the electromagnetic cross section by more than 1,000 times. What makes that possible is topology, an area of study that focuses on properties that are preserved when an object is continuously deformed — for example, stretched or bent. A newly discovered topological property of light could dramatically change the manipulation of light scattering.

“As a result of that, we could decouple the relationship between the wavelength and the cross section,” he says.

Frequency, wave vector, polarization and phase are fundamental properties often used to describe a photonic system, says Ling Lu, one of the paper’s co-authors and a professor in the Chinese Academy of Sciences Institute of Physics and the Beijing National Laboratory for Condensed Matter Physics.

Photo: Ming Zhou

Ming Zhou

“Over the past few years, topology has emerged as another indispensable degree of freedom — thus opening a path toward the discovery of fundamentally new states of light and possible revolutionary applications,” he says.

Topological photonics could have applications in fields that require concentrated light in a small area, such as medical imaging, in photodetectors, radio-frequency military communications, and others.

“It also could be extended to electronic and acoustic systems, because they are all waves,” says Ming Zhou, a graduate student working with Yu and the paper’s lead author. “This topology may change some of the very fundamental things we have understood for many years.”

Other authors on the Nature Communications paper include Lei Ying of UW–Madison and Lei Shi and Jian Zi of the Department of Physics at Fudan University, Shanghai.

The research was funded in part through financial support from the U.S. Defense Advanced Research Projects Agency (YFA17 N66001-17-1-4049 and DETECT program).

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Breeding highly productive corn has reduced its ability to adapt  external link

Stuck where they are, plants have to adapt to their environments, responding to stresses like drought or pests by changing how they grow.

On a broader scale, crop breeders need to be able to develop new varieties that are adapted to a new location or changing growing conditions in the same area.

Both types of adaptation rely on a pool of possibilities, the combinations from which one can choose. For the individual plant, those possibilities depend on the genome it was born with. For breeders, that pool of possibilities is the whole range of genomes of cultivated crops, which they can blend together to create new varieties.

Photo: Natalia de Leon taking notes in cornfield

Natalia de Leon takes notes on experimental corn plots at the West Madison Agricultural Research Station. By measuring populations of corn plants across North America, de Leon and colleagues could test how the corn genomes responded to different growing conditions. Photo: cornbreeding.wisc.edu

Researchers at the University of Wisconsin–Madison wanted to know whether the last 100 years of selecting for corn that is acclimated to particular locations has changed its ability to adapt to new or stressful environments. By measuring populations of corn plants planted across North America, they could test how the corn genomes responded to different growing conditions. Writing Nov. 7 in Nature Communications, UW–Madison Professor of Agronomy Natalia de Leon, her student Joe Gage and colleagues at several institutions report that artificial selection by crop breeders has constricted the pool of possibilities for North American corn varieties.

They conclude that the existing corn varieties are strong and stable, but are less flexible in their ability to respond to various stresses. At the same time, these corn populations might have a reduced ability to contribute to breeding programs that seek to create new varieties adapted to novel environments.

“Over the last 100 years, people have definitely improved cultivars,” explains de Leon, the senior author of the new report. “What we were trying to do in this study is to measure whether by doing that we have also limited the ability of the genotypes to respond to environments when they change.”

Photo: Joe Gage measuring corn plants

Joe Gage is one of the researchers who found that the regions of the corn genome that have undergone a high degree of selection were associated with a reduced capacity of corn to respond to variable environments. Photo: UW-Madison Department of Agronomy

By intensively breeding for high yield, say, in Wisconsin, those plants might lose the flexibility to respond to environments that are very different from Wisconsin growing conditions. To test this idea, de Leon and her colleagues at 12 agricultural universities in the U.S. and Canada devised a large field trial with more than 850 unique corn varieties at 21 locations across North America. There were more than 12,000 total field plots where researchers measured traits like yield and plant height while recording weather conditions.

The massive experiment is only possible because of a collaboration that de Leon, UW–Madison agronomy Professor Shawn Kaeppler and others lead, called Genomes to Fields. The project stretches across 20 states and into Canada, providing precisely the range of different field conditions that is required to tease apart the different contributions of the genomes and environments to the final traits of corn that were used in the new study.

De Leon and her collaborators found that the regions of the corn genome that have undergone a high degree of selection — for example, gene regions that contribute to high yield in a particular location — were associated with a reduced capacity of corn to respond to variable environments than genomic regions that weren’t directly acted on by breeders. The upshot is that the modern corn varieties are very productive in the environments they are grown in, but might have a harder time handling changes in those environments.

“When you try to adapt cultivars to many different environments, you end up with plants that are not great anywhere.”

Natalia de Leon

“The data seem to point to the idea that by selecting genotypes that are better suited to be more productive, we are eroding variability that might be important as we move into a world where climate might be more erratic and where we might need to move cultivars into places where they haven’t been grown before,” de Leon says.

Yet this loss of flexibility is an inherent tradeoff for highly productive cultivars of corn, she says.

“When you try to adapt cultivars to many different environments, you end up with plants that are not great anywhere,” says de Leon. “The cost of maintaining this plasticity is at the detriment of maximum productivity.”

“So we have to strike the right balance in the long term,” she says.

This project was supported by the Agriculture and Food Research Initiative Competitive Grants Program (grant number 2012-67013-19460) from the USDA National Institute of Food and Agriculture, USDA Hatch program funds to multiple researchers in this project, NSF Plant Genome Research Project #1238014, the USDA-ARS, the Ontario Ministry of Agriculture, Food and Rural Affairs, the Iowa Corn Promotion Board, the Nebraska Corn Board, the Minnesota Corn Research and Promotion Council, the Illinois Corn Marketing Board, and the National Corn Growers Association.

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UW scientists create a recipe to make human blood-brain barrier  external link

The blood-brain barrier is the brain’s gatekeeper. A nearly impenetrable shield of cells, it keeps toxins and other agents that may be in circulating blood from gaining access to and harming the brain.

A critical anatomical structure, the barrier is the brain’s first and most comprehensive line of defense. But in addition to protecting the brain, it also is involved in disease and effectively blocks many of the small-molecule drugs that might make effective therapies for a host of neurological conditions, including such things as stroke, trauma and cancer.

Graphic: Picture of how stem cells are turned into the blood-brain barrier

A team of UW-Madison researchers has developed a tightly defined, step-by-step process to turn multipurpose stem cells (top) into the cells that make the human blood-brain barrier (bottom), the anatomical feature that protects our brain from toxins and other threats that may be in circulating blood. Image: Tongcheng Qian, UW-Madison

Rudimentary models of the barrier have been created in the laboratory dish using human stem cells, but such models have depended on mixing a cocktail of cell types to elicit the complex chemical interplay that directs blank slate stem cells to become the endothelial cells that make up the blood-brain barrier.

In a report published this week (Nov. 8, 2017) in Science Advances, researchers from the University of Wisconsin-Madison detail a defined, step-by-step process to make a more exact mimic of the human blood-brain barrier in the laboratory dish. The new model will permit more robust exploration of the cells, their properties and how scientists might circumvent the barrier for therapeutic purposes.

Photo: Sean Palecek

Sean Palecek

“The main advance is we now have a fully defined process that uses small molecules to guide cells through the developmental process,” says University of Wisconsin-Madison Professor of Chemical and Biological Engineering Sean Palecek of the method that substitutes chemical factors for cells to push stem cells to become the brain endothelial cells that compose the blood-brain barrier. “It is fully defined. We know what components are acting on the cells” and at what stages of development.

To develop the new method for making the cells, Palecek collaborated with the laboratory of UW-Madison chemical and biological engineering Professor Eric Shusta. Tongcheng Qian, a Wisconsin postdoctoral researcher in chemical and biological engineering, led the study. The team has applied for a patent on the process through the Wisconsin Alumni Research Foundation, the not-for-profit organization that manages UW-Madison intellectual property.

Photo: Eric Shusta

Eric Shusta

Photo: Tongcheng Qian

Tongcheng Qian

In stem cell science, directing stem cells to become any of the hundreds of cell types that make up the human body is often as much art as science. By identifying specific chemical molecules that can chaperone the cells through the various stages of development to become the brain endothelial cells, the Wisconsin team, in effect, provides a recipe to standardize making the cells in quantities useful for research and things like high-throughput drug screens.

“Other approaches require mixing and co-culture of other cell types,” explains Shusta. “This will enable the non-expert to deploy the model. It’s an off-the-shelf recipe.” Using induced cells, adult cells from patients, which are reprogrammed to an embryonic stem cell-like state, will also allow researchers to better understand the etiology and progression of a variety of neurological disorders. Things like infections of the brain and multiple sclerosis may be better understood at their onset.

“It standardizes the approach. It can be applied to a broader portfolio of cells. We can really investigate disease,” says Palecek, noting that an ability to track cells as they progress through various phases of development can help scientists see the cascade of cellular events that occur as neurological conditions manifest themselves.

The new method, he adds, will also allow industry to scale up production of the brain endothelial cells for drug discovery. By exposing cells to various agents, researchers can assess toxicity and effect of promising therapies.

This work was supported by the National Institutes of Health (grants R21 NS085351, R01 NS083699, and R01 EB007534) and the Takeda Pharmaceuticals New Frontier Science Program.

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New model reveals possibility of pumping antibiotics into bacteria  external link


Biochemistry professor Katherine Henzler-Wildman in the National Magnetic Resonance Facility at Madison, housed in UW–Madison’s Department of Biochemistry. UW–Madison/Robin Davies

Researchers in the University of Wisconsin–Madison Department of Biochemistry have discovered that a cellular pump known to move drugs like antibiotics out of E. coli bacteria has the potential to bring them in as well, opening new lines of research into combating the bacteria.

The discovery could rewrite almost 50 years of thinking about how these types of transporters function in the cell.

Cells must bring in and remove different materials to survive. To accomplish this, they utilize different transporter proteins in their cell membranes, most of which are powered by what is called the proton motive force. The proton motive force is directed toward the inside of the cell in bacteria, which means that protons naturally want to move in to the cell from the outside and do so if there is a pathway for them. These transporters allow the measured movement of protons into the cell — and in exchange for protons moving in, drug molecules get expelled.

It was long thought that this coupled exchange of protons (in) and drugs (out) by the transporter was very strict. However, in a study published today (Nov. 7, 2017) in the journal Proceedings of the National Academy of Sciences, UW-Madison biochemistry professor Katherine Henzler-Wildman and collaborators at the Washington University School of Medicine in St. Louis have found that for E. coli’s small multidrug resistance transporter, called EmrE, proton and drug movements are not as strictly coupled. This transporter can actually also move drugs and protons across the membrane in the same direction, as well as the opposite direction — introducing the option of moving molecules both into or out of the cell.

A transporter protein — called EmrE, shown in purple and green — in the cell membrane of E. coli bacteria can be switched between two conformations in order to pump molecules (such as antibacterial drugs) out of or into the cell. Image courtesy of Katherine Henzler-Wildman/UW–Madison

This minor detail has big implications, the researchers say. The models scientists have used for almost 50 years to visualize how these transporters work does not account for the new data. It also means that it might be possible for drugs to be pumped into the cell.

“The long-term implications are that this multi-drug transporter is reversible,” Henzler-Wildman says. “So instead of pumping drugs out to confer resistance, you have the possibility that you could use it to pump drugs in to kill bacteria. Drug entry is a big problem, so this is a new area to explore.”

She adds that this study and her previous work suggest that by manipulating the environmental conditions or the drug itself, the researchers may be able to control not only the rate of the transport but also its direction — at least in test tubes in the lab. Trying to confirm this in bacteria is one of the next steps in their research, she says.

“We started with a very basic science question of ‘how do these transporters work?’ and have stumbled upon this really translational direction,” she says. “People have been trying to target these kinds of pumps to stop antibiotic resistance to make antibiotics that we already have effective again. This suggests that you might be able to not just stop it but actually use these pumps to drive drugs into the cell as a new drug entry mechanism.”

This particular transporter is found in many bacteria. Surprisingly, scientists don’t yet know its real function in the cell. While it does pump out antibiotics, it is not the main transporter that aids E. coli in antibiotic resistance, and it’s possible it has other purposes still undiscovered. They have only found that is transports a large number of molecules from dyes to antibiotics.

“Bacteria are constantly at war with each other, so maybe it does play a role in drug resistance,” Henzler-Wildman says. “But it could also transport something else we haven’t tested, or maybe it works in pH resistance. We haven’t narrowed it down yet.”

“Having to rework the model and essentially rewrite the textbook on what we knew about the transporters will really change the way we think.”

Katherine Henzler-Wildman

Traditionally, the model used to describe this transporter was the “pure-exchange model,” which required the strict, regimented movement of protons and the drug in opposite directions. However, the reality of this process follows the mantra of “life is messy.”

Henzler-Wildman is proposing a new model called the “free-exchange model,” where the combinations and direction of transport are much more flexible with many more options than previously thought. They used magnetic resonance data to visualize these specific and previously unknown movements of the transporter. Then they studied how exactly the transporter responds in the test tube when, for example, it’s exposed to antibiotics, in order to confirm it works the way the structures showed.

“Having to rework the model and essentially rewrite the textbook on what we knew about the transporters will really change the way we think,” she says. “I’m actually going to teach this paper in our intro graduate course because it’s such a good story of how having a model in your head can limit your thinking and experiments and you really miss important things.”

This research was supported by Institutes of Health Grant 1R01GM095839, National Science Foundation graduate research Fellowship DGE-1143954, and a Mr. and Mrs. Spencer T. Olin fellowship for Women in Graduate Study.

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