Image made of chemo drug binding to DNA

INDIANAPOLIS, March 20 (UPI) -- A team of U.S. scientists has created the first three-dimensional image of how a chemotherapy agent targets and binds to DNA.

Researchers from the Indiana University School of Medicine and the Purdue University School of Science said their achievement might lead to the development of better chemotherapy drugs.

Using X-ray crystallography, the scientists produced the first 3-D molecular level images of bleomycin bound to DNA. X-ray crystallography is a widely used analytical technique in which X-rays are directed through crystals and results are deduced from the pattern of diffraction of the X-rays, the scientists said.

"Our 3-D picture of the structure of bleomycin gives us a much better understanding of exactly how the drug interacts with the DNA so we can begin thinking about engineering a better drug, with less toxicity," said Associate Professor Millie Georgiadis, co-senior author of the study with Professor Eric Long. "Since it's a DNA targeting agent, there's no limit to what type of cancers we could target with bleomycin if we can decrease the toxicity."

The study appears in the online early edition of The Proceedings of the National Academy of Sciences.

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63-year-old solves riddle from 1970

Israeli mathematician unravels puzzle that baffled scientists for decades

JERUSALEM - A mathematical puzzle that baffled the top minds in the esoteric field of symbolic dynamics for nearly four decades has been cracked — by a 63-year-old immigrant who once had to work as a security guard.

Avraham Trahtman, a mathematician who also toiled as a laborer after moving to Israel from Russia, succeeded where dozens failed, solving the elusive "Road Coloring Problem."

The conjecture essentially assumed it's possible to create a "universal map" that can direct people to arrive at a certain destination, at the same time, regardless of starting point. Experts say the proposition could have real-life applications in mapping and computer science.

The "Road Coloring Problem" was first posed in 1970 by Benjamin Weiss, an Israeli-American mathematician, and a colleague, Roy Adler, who worked at IBM at the time.

For eight years, Weiss tried to prove his theory. Over the next 30 years, some 100 other scientists attempted as well. All failed, until Trahtman came along and, in eight short pages, jotted the solution down in pencil last year.

"The solution is not that complicated. It's hard, but it is not that complicated," Trahtman said in heavily accented Hebrew. "Some people think they need to be complicated. I think they need to be nice and simple."

Weiss said it gave him great joy to see someone solve his problem.

Stuart Margolis, a mathematician who recruited Trahtman to teach at Bar Ilan University near Tel Aviv, called the solution one of the "beautiful results." But he said what makes the result especially remarkable is Trahtman's age and background.

"Math is usually a younger person's game, like music and the arts," Margolis said. "Usually you do your better work in your mid 20s and early 30s. He certainly came up with a good one at age 63."

Adding to the excitement is Trahtman's personal triumph in finally finding work as a mathematician after immigrating from Russia. "The first time I met him he was wearing a night watchman's uniform," Margolis said.

Originally from Yekaterinburg, Russia, Trahtman was an accomplished mathematician when he came to Israel in 1992, at age 48. But like many immigrants in the wave that followed the breakup of the Soviet Union, he struggled to find work in the Jewish state and was forced into stints working maintenance and security before landing a teaching position at Bar Ilan in 1995.

The soft-spoken Trahtman declined to talk about his odyssey, calling that the "old days." He said he felt "lucky" to be recognized for his solution, and played down the achievement as a "matter for mathematicians," saying it hasn't changed him a bit.

The puzzle tackled by Trahtman wasn't the longest-standing open problem to be solved recently. In 1994, British mathematician Andrew Wiles solved Fermat's last theorem, which had been open for more than 300 years.

Trahtman's solution is available on the Internet and is to be published soon in the Israel Journal of Mathematics.

Joel Friedman, a math professor at the University of British Columbia, said probably everyone in the field of symbolic dynamics had tried to solve the problem at some point, including himself. He said people in the related disciplines of graph theory, discrete math and theoretical computer science also tried.

"The solution to this problem has definitely generated excitement in the mathematical community," he said in an e-mail.

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Margolis said the solution could have many applications.

"Say you've lost an e-mail and you want to get it back — it would be guaranteed," he said. "Let's say you are lost in a town you have never been in before and you have to get to a friend's house and there are no street signs — the directions will work no matter what."

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What Does a Plant Sound Like?

Researchers have developed a computer algorithm that can identify some plant species according to their unique sonar echoes. The experiments were meant to help biologists understand how bats find their favorite fruits or insects, but the research might also help engineers design high-speed systems to identify everything from widgets on conveyor belts to faces in crowds.

Bats might be legally blind, but they can fly straight to a desired fruit tree, even one growing amid dense foliage. They do so using a process called echolocation, in which they send out a series of chirps and then listen very carefully to the returning echoes. Inspired by this ability, researchers in Tьbingen, Germany, decided to see if they could invent an artificial system that would perform the same task.

First, the team developed data sets called spectrograms by bouncing sonar signals off five kinds of plants, including spruce trees and black thorn bushes. The researchers then characterized the echo response time and frequency of the resulting sound reflection patterns, which varied according to the number and size of the branches and leaves on each plant. The resulting computer program, says biophysicist and lead researcher Yossi Yovel of the University of Tьbingen, could distinguish similar plants with "surprisingly high accuracy." Eventually, the team was able to achieve near-100% success in identifying all five plant species used in the tests, as reported today in PLoS Computational Biology.

The findings will be valuable not only in understanding how bats echolocate, says Yovel, but they should help humans as well. The vast majority of remote-sensing algorithms are based on vision, he says, so if the sonar algorithm can be perfected, one of its advantages will be the ability to function in low light or darkness. (Infrared can't deliver the same degree of resolution.) That could be useful in picking out a crime suspect walking along a dark city street or hiding amid a crowd on a darkened mass-transit platform.

The research could turn out to be "major," says computational biologist Sorin Istrail of Brown University. The idea that a simple algorithm could provide a way to extract a meaningful model for bat echonavigation through tree environments is "remarkable," he says, and could lead the way to practical advances in the machine-learning field. And neuroethologist Steven Phelps of the University of Florida, Gainesville, says the research confirms that subtle differences in the qualities of echoes are enough for a bat to tell a spruce tree from a birch tree. "When we say apples and oranges, we generally assume the differences are obvious," he says, but "I can't imagine having to listen for them."

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