New technology at Tufts University’s Center for Scientific Visualization is enabling researchers to translate the most abstract, complex scientific concepts into clearer, more precise 3-dimensional images than conventional visualization systems can create. Funded by a $350,000 grant from the National Science Foundation, Tufts’ new 14-foot by 8-foot visualization display offers a combination of advanced features found nowhere else in New England and in only a few other installations in the country. Its application will further Tufts’ research and educational programs in diverse disciplines, from mathematics and physics to human factors engineering, and even drama and dance. Brain’s Untapped Capacity for Visuals “Users will be able to manipulate, simulate, touch and literally immerse themselves in data in a way they never have been able to before,” said Amelia Tynan, vice president and chief information officer and co-principal investigator on the grant. Visualization is built on the age-old premise — borne out by modern cognitive science — that pictures say as much as, or even more than, words. The human brain has a powerful, often underutilized capacity to process visuals, noted Robert Jacob, computer science professor and co-principal investigator on the project. A large portion of the brain processes visuals, and visualization technology puts that ability to work. “The brain absorbs a lot more information when it’s presented in pictures rather than in stacks of data from a computer,” Jacob said. This, he says, enables researchers and students to recognize things more quickly and also develop insights about what’s going on with the data. Unusual Combination of Technologies While visualization is widely used in science, Tufts’ “VisWall” offers unusually robust capabilities by combining advanced features not typically found together. Housed at Tufts’ School of Engineering but available to the entire university, the seamless wall features a high resolution display system that uses rear projection in order to enhance the amount of detail that is visible. Most visualization systems use several projectors at once or multiple, tiled screens to display images. Tufts’ uses just a single screen with close to 9 megapixels resolution (4,096 x 2,169 pixels) and two projectors (with overlapping fields of projection) to create high- resolution images and animation. By using a single screen and two projectors, Tufts is able to produce ultra-high resolution images — including 3-D images — that appear smoother and without seams. Images projected at a higher resolution reveal fine, minute details that would be imperceptible on a screen with fewer pixels or tiled images. The VisWall’s projectors are equipped with Infitec filters to minimize ghosting, in which an image appears to include elements of another image. Ghosting is a common drawback with conventional polarized filters. In addition, the Tufts system can combine the sense of touch with that of sight through haptic devices that convey varying levels of resistance to the user when he or she touches graphical objects on the display wall. This also allows Tufts researchers to create virtual environments, such as the human body for surgical simulations that can be physically manipulated and transformed. Order in Chaos Tufts faculty have already discovered applications of the new technology. Mathematics Professor Boris Hasselblatt made a surprising find while viewing a mathematical model of butterfly populations as they fluctuated through successive generations. The model, used for research in dynamical systems theory, is based on a simple formula and is well-known to anyone familiar with chaos theory. Visualizing the large population dataset with the 14-foot-wide, high-resolution graphical display enabled Hasselblatt to detect anomalies impossible to perceive with conventional displays: subtle traces of curving lines that he said indicated irregularities in variations in the population. The lines extended over different areas of the model and then converged at one distinct point. Hasselblatt has looked at smaller images of this classic model many times during the last 20 years but had never recognized this convergence. He has not yet determined the implications of this discovery, but he said the pattern reflects order in what mathematicians have always thought to be a progression of chaotic cycles. “The pattern is so subtle that it’s imperceptible but in this rendition the resolution is fine enough that I can easily see it,” he said. Bruce Boghosian, chairman of the mathematics department at Tufts and principal investigator on the NSF grant, said that the VisWall will benefit his study of fluid dynamics. Visualization capabilities can help him and his fellow researchers better understand fluid flow. “You can go right up to streamlines in a fluid or dig into a reservoir and see which way it’s flowing,” said Boghosian. “That’s the direction we would like to move in. You can imagine all kinds of other uses for something like that.” Virtual Surgery The VisWall will also aid Mechanical Engineering Assistant Professor Caroline Cao. Her goal is to develop more robust laparoscopic surgical training systems in which 3-D computer simulations enable surgeons in training to feel as well as see. She and her team, including senior Kyle Maxwell, have already developed software that enables users to remove a “tumor” during a simulated procedure. With the haptic device, these virtual surgeons receive force feedback when touching a hard surface, such as a tumor or bone, and a soft, deformable surface, such as tissue. The reaction is determined by the parameters provided by the model, which is based on real material properties. Cao, who is director of the human factors program in the School of Engineering, said she wants to develop more anatomical features in the models. She also hopes to develop software that will simulate more complicated virtual procedures like heart surgery and colonoscopy. The VisWall’s size, resolution and 3-D capability will greatly help in her work. “Imagine the difference between simulating a virtual environment on a computer screen and one on a visualization wall — the difference is tremendous,” she said. “That’s what large-scale visualization gives us, a capacity to create a richer immersion experience.” From Particle Physics to the “Lord of the Rings” Similar benefits could be gained by physicist Austin Napier. His work in high energy physics relies on the ability to process huge streams of data from organizations like Switzerland’s CERN, the world’s largest particle physics laboratory. Tufts’ VisWall will enable him to visualize on a single display what would otherwise require multiple computers. Tynan said she expects the VisWall to become a resource for the broad range of academic disciplines at Tufts. She envisions scientists and engineers collaborating with faculty from the arts or humanities. Boghosian brings up the example of the character Gollum in the “Lord of the Rings.” Actor Andy Serkis’ movements were tracked and translated to the digital rendering of the creature in the film. Similar technology is now available through the VisWall, which goes beyond traditional 3-D rendering to create a true virtual reality environment. “Imagine taking the ability to do something like that and applying it to drama and dance,” Boghosian mused. “Imagine taking the ability to do something like that and trying to use it for facial recognition or occupational therapy or many other fields. We haven’t really even begun to explore those kinds of things yet.” [Alex Reid @ Tufts University]

Deadly Genetic Disease Prevented Before Birth In Zebrafish
By injecting a customized “genetic patch” into early stage fish embryos, researchers at Washington University School of Medicine in St. Louis were able to correct a genetic mutation so the embryos developed normally. The research could lead to the prevention of up to one-fifth of birth defects in humans caused by genetic mutations, according to the authors. Erik C. Madsen, first author and an M.D./Ph.D. student in the Medical Scientist Training Program at Washington University School of Medicine, made the groundbreaking discovery using a zebrafish model of Menkes disease, a rare, inherited disorder of copper metabolism caused by a mutation in the human version of the ATP7A gene. Zebrafish are vertebrates that develop similarly to humans, and their transparency allows researchers to observe embryonic development. Children who have Menkes disease have seizures, extensive neurodegeneration in the gray matter of the brain, abnormal bone development and kinky, colorless hair. Most children with Menkes die before age 10, and treatment with copper is largely ineffective. The research is published this month in the Proceedings of the National Academy of Sciences’ advance online edition. The development of organs in the fetus is nearly complete at a very early stage. By that time, the mutation causing Menkes disease has already affected brain and nerve development. Madsen and Bryce Mendelsohn, also an M.D./Ph.D. student at the School of Medicine, wondered if they could prevent the Menkes-like disease in zebrafish by correcting genetic mutations that impair copper metabolism during the brief period in which organs develop. Both students work in the lab of Jonathan D. Gitlin, M.D., the Helene B. Roberson Professor of Pediatrics at the School of Medicine and director of Genetics and Genomic Medicine at St. Louis Children’s Hospital. The researchers used zebrafish with two different mutations in the ATP7A gene, resulting in a disease in the fish that has many of the same characteristics of the human Menkes disease. Madsen designed a specific therapy to correct each mutation with morpholinos, synthetic molecules that modify gene expression. The zebrafish embryos were injected with the customized therapy during the critical window of development, and the researchers found that the zebrafish hatched and grew without any discernable defects. “This method of copper delivery suggests that the prevention of the neurodegenerative features in Menkes disease in children may be possible with therapeutic interventions that correct the genetic defect within a specific developmental window,” Madsen said. The genetic mutations Madsen and the researchers worked with are caused by splicing defects, or an interruption in genetic code. The morpholinos prevent that interruption by patching over the defect so the gene can generate its normal product. “Consider the genetic code as a book, and someone has put in random letters or gibberish in the middle of the book,” Madsen said. “To be able to read the book, you have to ignore the gibberish. If we can make cells ignore the gibberish, or the splicing defect, the fetus can develop normally.” Up to 20 percent of genetic diseases are caused by splicing defects, Madsen said, so this treatment method could potentially be used for many other genetic diseases. “The idea is that we can modify the treatment to target a specific mutation and design molecules to alter gene function in the same way the morpholino oligonucleotides can,” Gitlin said. The work is an important step toward personalized medicine, which can tailor treatment to an individual’s genetic makeup. “Eventually we would like to know each person’s genome sequence so we know what mutations each person has that may lead to disease,” Gitlin said. “That way, you don’t get a drug for cancer that works against any kind of cancer, you get a drug for the specific mutation that causes your cancer. That’s what personalized medicine is all about.” Beth Miller @ Washington University in St. Louis]

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