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Life and Limb: Departments Collaborate on $2 Million Grant That Will Pave the Way for Wound-Healing Therapies
Story by Kathryn Wallingford
Photo by Mark Cornelison
April 2010
This article was originally published and produced by the University of Kentucky College of Arts and Sciences in their Spring 2010 publication of Ampersand magazine. Reproduced with permission. The original article can be found at the College's website at the following link. Link
Two UK faculty members (Voss and Stromberg) associated with the KY NSF EPSCoR RII effort in Ecological Genomics recently received a $2M award from the Department of Defense to study genetic properties related to limb and tissue regeneration.
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The United States Department of Defense recently awarded University of Kentucky professors Randal Voss and Arny Stromberg a $2 million grant entitled “Signaling Network Interactions Controlling Mouse and Salamander Limb” to develop methods for inducing regenerative responses in mammalian limbs. Using a systems approach, Voss, a biology professor, and Stromberg, the chair of the Statistics Department, will undertake the most complicated models they have yet to face and pave the way for exciting new possibilities for wound-healing therapies. After using genomic tools to determine how salamanders regenerate limbs and how mice respond to limb injury, Voss and Stromberg will build models of the regenerative process by detailing how genes interact during regeneration. Information generated from these models will guide experiments performed by collaborators at Tulane University and the University of California, Irvine. Ultimately, the coupled process of modeling and experimentation will yield the best approach for implementing mammalian regenerative responses. Ampersand recently had the opportunity to sit down with these two professors as well as the chair of the biology program, Vincent Cassone, to learn more about the implications of this grant, the significance of collaborative research at the University of Kentucky and the Biology Department's commitment to biomedical research.
The connection between the Department of Defense, a biologist and a statistician is very curious. Can you tell us more about this collaborative effort?
VOSS: I collaborate with a couple of researchers [Ken Muneoka at Tulane University and David Gardiner at the University of California, Irvine] that use the salamander model and a mouse model for regenerative research. They have been funded by the Department of Defense for the last five years on a project to stimulate a regenerative response within a mammalian digit. They use a salamander called the Mexican axolotl to learn about regeneration. We maintain at UK the only large captive breeding colony of axolotls in the world. This is funded by NSF [the National Science Foundation].
Salamanders have an ability, which is widely recognized by biologists, to regenerate complex body parts, including limbs, spinal cord, and part of the brain - almost everything. Over the last eight years, NIH [the National Institute of Health] has made an investment through my lab to start developing genome resources to make a salamander model so we can learn something about regeneration at the molecular level. We have hundreds of years of descriptions of salamanders regenerating complex body parts, but we do not know what is happening inside the cells of salamander tissues - arms, legs, heart - that can regenerate. In particular, we do not know what genes are doing during regeneration.
STROMBERG: We will use statistical pattern matching to identify sets of genes that differentiate a regenerative response from a non-regenerative response. Many biologists use cluster analysis to group genes with similar expression patterns. Typically, groups of genes identified in this way are difficult to interpret biologically because they contain many false positives. Statistical pattern matching eliminates most of the false positives, making the group of genes much easier to interpret.
CASSONE: The collaboration also says something important about UK. It is an institution that is committed to biomedical research, and yet involves a basic biology department where researchers study the axolotl, wild bird species, wild fish species, and things that are not typically employed in medical research. It is a testament that by using these specialized non-traditional models, we can provide insight in real biomedical issues and really apply these to therapies.
STROMBERG: We are all in the same college (A&S), but we are working on a project that also interests the UK Medical Center. One of the things that UK does better than other places is collaboration across the university. This project might have never have happened if we were at a different university. The fact that we can do this is special.
What are the immediate and long-term goals [sic] for this project?
VOSS: The genome of a salamander is so large that it would be very difficult to sequence, even with next generation sequencing technologies that are available now. So, the first short-term goal is to sequence in-depth mRNA transcripts from regenerating salamander limbs and build protein models for all 20,000 genes. We have already made great progress. The second step is to make the tools to measure the abundance of mRNAs, which will tells us how genes are expressed. These tools are available for mice. There is an interesting mouse model where early in development the mouse can regenerate in the same way a salamander regenerates its limb. It even makes a blastema [a mass of cells capable of growth and regeneration into organs or body parts]. It is a very limited regenerative response, but provides a good model for engineering, using information from the salamander regeneration model.
In a systems approach, you first recognize that the problem is complicated and has a lot of components and that you need an appropriate approach to deal with that complexity. After you build a model of it, you need to go in and perturb some aspects of the model that you are most interested in. And this is where it becomes a flow of information between the groups. We start by making the model and then we give our collaborators the model. They think of ways to experimentally perturb the model to engineer, for example, a regenerative response in the mouse or a non-regenerative response in the salamander. We re-make the models after the perturbation and this informs the next set of experiments.
Can you tell us more about the significance of each of your approaches and why they are so novel?
STROMBERG: The idea is to understand the complexity of the situation. How can we better understand how all these genes work together? Statistically, we are hoping to figure out which genes follow the same patterns. We are trying to interpret gene expression over time. Essentially, the whole aim of the study is to study how the genes change expression as regeneration is happening, and to model this has not been done before. We want to group the known genes with the unknown genes with the hope that with statistics, we can determine which ones are biologically interesting and involved with the regeneration process.
VOSS: The project will deliver the most detailed models of salamander limb and mouse digit regeneration ever developed. We are originating a systems biology approach to a complicated biological problem that has clear human health implications.
You all are very accomplished in your fields. How does this grant compare to other research grants you have worked on? What makes this so exciting?
STROMBERG: Well, it's more complicated. These are more complicated models that we are trying to put together than we have ever done before. And more time points. I think we have 13. I think the most we have looked at in other studies within the university is five.
Can you tell us what you mean by “time points?”
VOSS: So, temporally it will take the salamander 70 days to regenerate its arm. What we are looking at is an early 13-day period. Within 7-8 hours after an arm has been cut off, epithelial cells cover the wound thousands of times faster than happens in mammals. During this first 13 days the cells are being reprogrammed to become the blastema, which is needed to orchestrate regeneration.
STROMBERG: The key is we have more time points focused around the time when the important decisions are being made within cells. With more time points, we get a better idea of what is happening as cells are being reprogrammed. It's just more information. We have more information about the genome, a better gene chip, and with more time points, we will be able to tell better what is happening.
Scientists at the University of Kentucky follow an important legacy. As you very well know, the biological building at UK is named after Thomas Hunt Morgan, who graduated from the University of Kentucky in 1886 and later won the Nobel Prize for his developments in understanding the role chromosomes play in heredity. Although he is best known for his accomplishments in the field of genetics, in his 1901 publication, “Regeneration,” Morgan emphasized the significance of regenerative capacities of organisms and the implications this had for the field of biology. How does it feel to be a part of this legacy?
CASSONE: That is interesting. My Ph.D. advisor and I are now studying something completely different from Thomas Hunt Morgan. However, his thesis advisor actually studied with a student of Morgan. So, there are several legacies. They are the legacies of biology and legacies of genetics. But the students that Morgan actually trained ended up being the foundation of much of modern biology in diverse areas. I am essentially a neuroscientist, and yet I can follow my background back to Thomas Hunt Morgan. So, he was an incredibly prolific scientist in context of his own research, but also in having people who trained people, who trained people, who trained people.
On that note, scientists have come a long way since Morgan's first work with Drosophila. What, in your minds, have been the biggest milestones in science that have allowed you to ask the rigorous questions that you are asking today?
CASSONE: Really, biology is the most dynamic scientific discipline. There is more integration in biology with fields such as genetics, neurobiology and ecology than we can analyze. And that is one of the reasons many of us have developed collaborations with people like Arny. Biologists have collected sequences of some 200 species and are annotating more, trying to compare them, looking at how they are dynamically expressed, and, frankly, our personal brains are not big enough to grasp the amount of information that is being collected. As biologists collect information, we have to develop new ways to understand biology. The biggest milestone is probably ...
STROMBERG: ... the proliferation of information.
CASSONE: Yes, including the identification of the structure of DNA, the identification of the gene as the unit of transcription and the human genome project.
VOSS: The human genome project spun off a lot of other systems biology projects.
CASSONE: The truth is the human genome project has created a way of thinking about biology that we have never thought about.
New, innovative genetic approaches are an important aspect of research at the University of Kentucky. As university scientists continue to make important contributions to the field of science and their understanding of regeneration, what is the next step for the fields of biology and statistics following this trajectory?
STROMBERG: Data analysis cannot keep up with the amount of information being generated. We can have the fastest computers in the world and the best statisticians, but there will always be more data than we can look at. It's just impossible. Important decisions have to be made about what data to look at. The DOD has made a decision to look at this data because it has the potential to be very useful.
In this edition of Ampersand, we are highlighting regeneration. What does this word mean to biologists and statisticians?
STROMBERG: We want to get the cells to do what we want to them to do.
VOSS: You want to introduce a true regenerative response inside an individual. You do not want to have to invasively go in and engineer a regenerative response by transplanting tissues or organs. That is what we are really trying to work at: the induction of a true regenerative response.
UK's Center for Advanced Materials Producing Liquid Helium
by Kathryn Wallingford
April 2010
This article was originally published and produced by the University of Kentucky College of Arts and Sciences. Reproduced with permission. The article can be found at the College's website. Link
The Center for Advanced Materials sponsored by KY NSF EPSCoR can now produce its own liquid helium. UK scientists use 400 to 500 liters per week and were paying around $10 per liter.
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Beneath earth's impermeable rock layers, helium is generated from the decay of radioactive materials. Once released, helium, the second lightest element on earth, escapes from our atmosphere - too light for gravity to hold, helium floats away. Like coal and oil, the supply of helium is finite and some predict as soon as the year 2015, the earth's supply will have vanished.
Like coal and oil, the supply of helium is finite and some predict as soon as the year 2015, the earth's supply will have vanished.
Although the declining supply of helium might not be as publicized as the earth's depletion of oil or other natural resources, its shortage has profound consequences. For helium serves purposes beyond supplying consumers with birthday balloons.
Whereas all other elements, such as water, freeze at extremely cool temperatures, helium is able to maintain its liquid state as temperatures approach absolute zero. This unique property makes liquid helium a vital factor for many applications, including cooling superconductors that are a key component for some of life's most basic luxuries, such as the production of flat-screen televisions, to more essential technologies, such as MRI and nuclear physics, low temperature condensed matter physics, and space technologies.
Fortunately, University of Kentucky Professor of Physics and Astronomy and the Director of the Center for Advanced Materials, Dr. Gang Cao has not only found a way to keep helium in earth's atmosphere, but in UK's laboratories. The University of Kentucky can now make its own liquid helium.
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Recently awarded a $ 4.5 million National Science Foundation EPSCoR (Experimental Program to Stimulate Competitive Research) grant, Cao helped establish the Center for Advanced Materials last year with the goal of not only discovering and improving new materials, but making the University of Kentucky a national player in condensed matter and materials research.“We have the intellectual asset at the university, now we need to build the infrastructure,” said Cao.
Securing a helium liquefier was a major step in building a more progressive infrastructure and putting the Center for Advanced Materials on the map. Relatively few research universities in the nation have such unique and innovative capabilities, and the University of Kentucky is one of them.
Cao has always been committed to the synthesis and application of materials research. However, he has often been frustrated with the lack of research and funding towards the production of new materials in the United States.
“There are many national labs that measure and characterize materials, but there are not parallel efforts to produce these materials,” said Cao. “You have to control materials,” he continued. “I have said this many times, if you control materials, you control technology. Now here at the University of Kentucky, we can do everything under the same roof.”
Besides distinguishing UK as a leader in condensed matter and materials research, the purchase of a helium liquefier has also given UK financial freedom.
In the past, Cao and his colleagues have purchased liquid helium from commercial vendors for a very high price. Over the last eight years, the cost of purchasing liquid helium has almost quadrupled, increasing from around $2 per liter to around $10 per liter.
“This facility has drastically reduced our dependence on commercial sources for liquid helium. This is particularly important in a time when the market becomes so unreliable,” said Cao.
Professors in the Department of Physics and Astronomy, including three new professors that were recently hired through the NSF EPSCoR grant, and Professors in UK's Department of Chemistry will take advantage of this new resource.
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Using recovered helium gas from individual labs in UK's Physics and Chemistry building, gaseous helium is initially collected into a holding tank. Then moving through two compressors and finally the liquefier, liquid helium is produced and ready to use for research. In just one hour, the UK's Department of Physics and Astronomy can produce up to 47 liters of liquid helium.
Typically using 400-500 liters per week, UK physicists and chemists are utilizing UK's generated liquid helium to cool superconducting magnets and better understand the physical properties of electronic materials, properties such as quantum oscillations, superconductivity, quantum Hall effect, and magnetism.
Whereas in the past the acquisition of helium from distributors could sometimes be undependable, let alone expensive, Cao said, “We have no excuses now. This is a big milestone for UK as well as the Center for Advanced Materials.”
In the next few years, Cao hopes the Center will be one of institutions that lead the nation in condensed matter and materials research.
Cao credits the advancements made thus far to the continued involvement of the UK's College of Arts and Sciences. “Their support has been crucial,” he said.
Two other items will soon be added to the Center for Advanced Materials to aid in their cutting-edge research. In April, the center will receive a Physical Properties Measurements System (PPMS) to conduct ultralow-temperature and high magnetic field studies. Soon after, the Center will purchase an X-ray Diffractometer for studying crystal structures.
NH EPSCoR and KY EPSCoR Sponsor SC09 Volunteer
April 2010
This article was originally published and produced by the New Hampshire EPSCoR Program. Link
Adam Villa, a computer science doctoral candidate at the University of New Hampshire, was selected from a pool of over 200 applicants to serve as a student volunteer at the 21st Annual Supercomputing Conference (SC09) in Portland, OR on November 14-20.
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Sponsored by the ACM SIGARCH and IEEE Computer Society, SC09 is an international conference focused on High Performance Computing (HPC), networking, storage and analysis. The conference featured the latest scientific and technical innovations from around the world, bringing together scientists, engineers, researchers, educators, programmers, system administrators, and managers. SC09 was a forum for demonstrating how these developments are driving new ideas, new discoveries and new industries with a special focus on HPC in support of bio-Computing, sustainability, and the 3D Internet.
Barbara A. Kucera, Deputy Director of Kentucky EPSCoR and SC09 Student Volunteer Co-chair said, “The contacts these students will make, the overall experience of being thrust into the heart of high performance computing, the unique behind the scene accessibility to leaders and speakers, and the exposure to state-of-the-art technology will provide opportunities that may not be realized for some time, but I am certain that SC09 will be an experience students will not soon forget.”
Funding to attend this conference was provided by both New Hampshire EPSCoR and Kentucky EPSCoR. Adam Villa said of his opportunity to volunteer at the conference, “I had a wonderful experience at the Supercomputing Conference. I was able to talk with fellow graduate students and researchers in my field of study. I learned about cutting edge new hardware and software technologies. I was able to attend several informative talks, tutorials and workshops dealing with topics related to my research and also new areas of computer science that I have never studied before. Overall my experience at SC09 was a great benefit to both my research and graduate education. I am very grateful for the travel grant awarded to me by EPSCoR, without which I would have never been able to attend.”
Image: Adam Villa pictured outside the Oregon Convention Center where the SC09 conference was held in November. (Courtesy Photo)
Not Just Blowing Smoke
by Robin Roenker
photos by Mark Cornelison
April 2010
This article was originally published and produced by the University of Kentucky College of Arts and Sciences. Reproduced with permission. The article can be found at the College's website. Link
Dr. Gang Cao and other UK faculty in the Departments of Physics, Chemistry and Engineering are leading an EPSCoR-sponsored effort to develop a Center for Advanced Materials (CAM). Their effort was recently detailed in an article published by the UK College of Arts and Sciences.
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The transistor is perhaps the most prolific and highly successful example of electronic material in action. It's the fundamental building block of today's electronic devices-from cell phones to iPods to personal computers.
Some have called the transistor the greatest invention of the 20th century. Its development and perfection over the last 60 years has largely been a result of the research and development work of condensed matter physicists-scientists who study the fundamental properties of solids and liquids. Their work to create and study new electronic and magnetic materials has yielded “the largest number of practical applications” of any subfield of physics, according to physics professor Gang Cao, who joined UK's Department of Physics and Astronomy in 2002.
Cao also points out that it is widely recognized that whoever discovers and controls the optimized synthesis of novel materials generally controls the investigation of their often unique properties and, ultimately, their successful integration into advanced technologies.
And what is to be the field's greatest contribution to the 21st century? Cao expects the University of Kentucky's Center for Advanced Materials at the forefront of charting that answer.
Launched last year thanks to a $4.5 million National Science Foundation EPSCoR (Experimental Program to Stimulate Competitive Research) grant, the center will position the University of Kentucky among the top university labs in the nation doing research in new materials synthesis and characterization, Cao said.
“Ultimately, we want to improve and discover new materials for future application,” he said. “That is our ultimate goal.”
Having worked for 12 years at the National High Magnetic Field Laboratory in Tallahassee, Fla., before coming to UK, Cao, along with many in his field, has noted that U.S. leadership in materials research has seriously eroded in recent years due to a growing shortage of scientists and engineers who possess skills in both the synthesis and characterization of new materials. “The current situation presents an urgent national challenge that could ultimately undermine our economic competitiveness if left unaddressed,” Cao stated.
By launching and directing the new Center for Advanced Materials at UK, he believes the University of Kentucky can establish a unique niche as a specialist in both the development of new materials and the analysis of their particular properties.
To do that, the center will draw on the expertise of UK's physics faculty already doing work in condensed matter physics-roughly a quarter of the department-as well as cross-disciplinary collaborations with researchers in UK's chemistry, engineering, and other departments.
The center's work emphasizes the creation of new materials in both bulk-single-crystal and thin-film forms having unusual electrical transport, magnetic, and optical properties. Once created, the center works to characterize the new materials' properties at extreme conditions, such as high magnetic fields, ultra low temperatures, and high pressures.
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“We have the advantage of an internationally recognized faculty-our human powers-as well as top-notch laboratory capacities to ensure high quality materials in single crystal form. That allows us to study the most intrinsic properties of the materials we produce,” Cao said.
The grant also includes funding for four new faculty positions, three of which have already been filled. And it's allowing the center to purchase cutting-edge equipment for, including a helium liquefier-a truly coveted asset few universities can boast. The machine will allow UK's faculty more steady and cost-effective access to the liquid helium they depend on as a cooling agent for their research, eliminating the need to purchase it from an outside source.
Thanks to his award as a 2009-10 UK Research Professor, Cao will be able to take some time off next year from teaching to focus on the continued establishment and advancement of the center.
Cao, a native of Wuhan, China, will also continue his work as chair of the international advisory committee helping oversee the creation of the National High Magnetic Field Center in Hefei, China. The project stems from an effort to enhance Chinese collaborative cooperation with the United States' National High Magnetic Field Laboratory he began while still working there over 10 years ago.
Graduate students coming to UK will have the benefit of expertise in both materials synthesis and characterization covering a broad spectrum of materials and experimental probes. All students will acquire hands-on experience in specialized investigations of structural and physical properties of materials using state-of-art equipment. “That is our major focus. We are materials scientists. We have to know how to make materials,” Cao said. “How can you be a capable materials scientist if you don't know how to make materials?”
“UK is already well positioned in this area,” he stated. “We have created a critical mass to be on top in a few years. There are only a handful of university labs in the country that have the ability to both develop and study new materials with a wide arrange of techniques and probes under one roof. This is going to be our whole advantage.”
Gates Cambridge Scholarship to Talented University of Kentucky Student
February 17, 2010
Lesley Mann receives the prestigious Gates Cambridge Scholarship.
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Kentucky NSF EPSCoR is developing the capacity to conduct outstanding research in the field of ecological genomics by providing state-of-the-art sequencing instrumentation, computational clusters, faculty support and financial assistance for student researchers over the next several years at the University of Kentucky (UK), Eastern Kentucky University and Northern Kentucky University. Much of the EPSCoR investment is focused on updating the Advanced Genetic Technologies Center (AGTC) housed in the Department of Plant Pathology at UK, which is directed by UK faculty member and KY NSF EPSCoR Initiative Leader, Dr. Christopher Schardl. The goal of the EPSCoR investment is to create the infrastructure necessary to enable nationally recognized research, faculty and students. One talented student is moving that agenda forward.
KY NSF EPSCoR would like to congratulate Ms. Lesley Mann on her 2010 Gates Cambridge Scholarship, which will allow her to pursue a Masters degree in Bioscience Enterprise at the University of Cambridge later this year. Gates Cambridge Scholarships are incredibly competitive with only about 100 being awarded each year. Lesley was one of 29 American students chosen for this honor, with her peers coming from undergraduate institutions such as Columbia, Harvard, Yale, Princeton, Stanford and MIT.
Lesley is finishing her B.S. in Agricultural Biotechnology at UK and has been conducting research with the Department of Plant Pathology over the last few years. She received a Beckman's Scholarship, which enabled her undergraduate research. Her research project involved conducting studies of gene expression in the symbiotic fungal endophyte, using quantitative polymerase chain reaction to determine how different genes were expressed at different developmental stages of the grass and fungus. Her study was key to the genomic and transcriptomic analysis of this symbiosis, which is responsible for imparting drought resistance and insecticidal properties in the grass. Lesley's Gates Cambridge Scholarship is recognized on the gatesscholar.org website at the following link:
http://www.gatesscholar.org/scholars/new_scholars_detail_2010.asp?ItemID=6151
What's Killing Our Bats - The Ecology of White-Nose Syndrome (WNS)
August 26, 2009
EPSCoR-supported researchers from Northern Kentucky University study WNS to find a way to save Kentucky's bat species.
In the winter of 2006 a large number of dead and dying bats were discovered within caves and mines in New York. Each of these infected bats had a characteristic white, powdery-substance around the muzzle and the disease affecting them was called White-Nose Syndrome (WNS). Bat species represent 20% of all mammalian species in North America and play a critical role in the processes of our ecosystem; a single bat can eat 600 insects in one night. These insects include agricultural pests and those capable of transmitting human disease. Since the initial discovery of WNS, the disease has spread throughout the northeast, affecting bats in nine states and leading to the death of over 1,000,000 bats; it has been calculated that represents 693 tons more insects this year than last.
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Elizabeth Shelly (NKU) and bat biologist Brooke Slack (KYDNR) collect baseline data on bats in Kentucky before the arrival of WNS. |
To date the cause of WNS appears to be a fungus, Geomyces destructans. This fungus appears to be primarily spread from bat to bat, although there is some indication that people visiting caves can also spread this pathogen. With WNS approaching Kentucky (G. destructans is presently in Virginia and West Virginia), researchers funded by the KY NSF EPSCoR (RII award 0814194) at Northern Kentucky University have been playing an important role in looking at ways to stop the spread of this organism. Dr. Hazel Barton and her research students Elizabeth Shelly and Alexis Henry, who specialize in cave microbiology, have been examining fungi in caves and methods of stopping the spread of this pathogen. Their work is currently examining how to decontaminate equipment used in caves and by bat researchers, including critical safety gear (such as ropes and harnesses) that can easily be damaged by chemical disinfection. As a result, Dr. Barton has been helping the US Fish and Wildlife Service develop decontamination guidelines for both recreational cavers and bat researchers. The team is also working on developing methods to protect the bats themselves, without impacting the normal microbial flora of these cave environments. To do this, Dr. Barton and her students will be traveling to New York to work with the Division of Natural Resources to examine bat decontamination protocols this winter.
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There are currently 45 bat species within the US, three of which are on the endangered species list. If WNS continues to spread unchecked, it is likely that we will witness the single largest mammalian extinction events in recent history and the largest wildlife crisis in 100 years. It is hoped that the work currently funded by EPSCoR will play a critical role in stopping the spread of this deadly pathogen and saving bats from extinction.
“Read more about Dr. Barton’s WNS research in an article by Discovery Magazine.” http://news.discovery.com/animals/bats-white-nose-syndrome.html