Fake Malaria Drugs Made In China: Tracking Down The Threat To Global Health

Daily Science Journal (Feb. 13, 2008) — A unique collaboration between scientists, public health workers and police has led to the arrest by the Chinese authorities of alleged traders of fake anti-malarial drugs in southern China and the seizure of a large quantity of drugs. The work, involving teams from across the globe, has highlighted both the growing threat posed by fake pharmaceuticals and the complexities of tracking down those responsible for the trade.

Counterfeit artesunate anti-malarial tablet with fake 'X-52' stamp as seen under UV light. (Credit: Newton PN, Fernandez FM, Plancon A, Mildenhall DC, Green MD,et al.)

Dubbed Operation Jupiter, the investigation was coordinated by the International Criminal Police Organisation (INTERPOL), the World Health Organization's Western Pacific Regional Office, and the Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme, in close cooperation with Chinese authorities. Scientists from 5 other laboratories analysed the composition of the fake drugs and their packaging.

Fake anti-malarial drugs are an increasingly serious problem, particularly in South-East Asia and Africa. In countries with a large burden of malaria, such as Myanmar (Burma), the Lao PDR, Cambodia and Viet Nam, as many as half of all artesunate tablets -- one of the most effective anti-malarial drugs -- is counterfeit.

Most of the fakes examined as part of Operation Jupiter contained no artesunate, and some contained a wide range of potentially toxic wrong active ingredients. Also of grave concern was the fact that counterfeiters sometimes included dangerously small amounts of artesunate in the tablets. This may be done to foil screening tests of drug quality, but these doses are too low to be efficacious, yet high enough to contribute to malaria parasites becoming resistant to this class of drugs.

"Artesunate, as part of artemisinin-based combination therapy, is vital for malaria treatment and is one of the most effective weapons we have against this terrible scourge," says Dr Paul Newton of the Wellcome Trust-University of Oxford SE Asian Tropical Medicine Research Programme. "Those who make fake anti-malarials have killed with impunity, directly through the criminal production of a medicine lacking active ingredients and by encouraging drug resistance to spread. If malaria becomes resistant to artesunate, the effect on public health in the tropics will be catastrophic."

In addition to analysing the chemistry of the samples, researchers used a technique known as forensic palynology to study pollen contamination within the fake tablets with the aim of tracking down the likely location of manufacture. The pollen evidence suggested that at least some of the counterfeit artesunate came from southern China, and this was supported by examination of the mineral calcite, found in some of the samples.

Armed with these findings by INTERPOL, Chinese authorities arrested a suspect in China's Yunnan Province in 2006. He is alleged to have traded 240,000 blisterpacks of counterfeit artesunate, enough to "treat" almost a quarter of a million adults with a medicine with no activity against a potentially fatal disease. Whilst the Chinese authorities were able to seize 24,000 of these packs, the remainder are alleged to have been sold at crossings on the border of Yunnan and Myanmar (Burma), accounting for almost a half of all blisterpacks of artesunate sold to the region.

The work of the Jupiter group highlights the need for more to be done internationally to support countries with a high prevalence of counterfeit anti-malarials in their attempts to combat this severe but under-recognised public health problem.

"Criminal investigations and legal action are important in disrupting and inhibiting the trade in fake medicines, but to be effective these will require financial support and resources," says Dr Newton. "Forensic tools may make it easier to identify the fake drugs and allow over-stretched police forces to focus on objective leads, greatly increasing the risks to counterfeiters of being caught. However, there are very few laboratories with the resources to perform detailed forensic chemistry or pollen analysis of fakes, particularly in the countries where they are most needed."

Journal citation: Newton PN, Fernandez FM, Plancon A, Mildenhall DC, Green MD,et al. (2008) A collaborative epidemiological investigation into the criminal fake artesunate trade in South East Asia. PLoS Med 5(2): e32.

Adapted from materials provided by Wellcome Trust.

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Nanosieves Save Energy In Biofuel Production

Daily Science Journal (Feb. 13, 2008) — A new type of membrane, developed by scientists of the University of Twente in The Netherlands, can stand high temperatures for a long period of time. This ‘molecular sieve’ is capable of removing water out of e.g. solvents and biofuels. It is a very energy efficient alternative to existing techniques like distillation.

The cylinder is the carrier of a hybrid membrane: a layer of about 100 nanometer thickness. The insert shows a close-up of the layer showing the organic links and pores. From the left of the tube, only water molecules leave the sieve. (Credit: Image courtesy of University of Twente)

Even after testing during 18 months, the new membranes prove to be highly effective, while having continuously been exposed to a temperature of 150 ºC. Existing ceramic and polymer membranes will last considerably shorter periods of time, when exposed to the combination of water and high temperatures. The scientists managed to do this using a new ‘hybrid’ type of material combining the best of both worlds of polymer and ceramic membranes. The result is a membrane with pores sufficiently small to let only the smallest molecules pass through.

Ceramic membranes, made of silica, degrade because they react with water and steam. In the new membrane, part of the ceramic links is therefore replaced by organic links. By doing this, water doesn’t have the chance to ‘attack’ the membranes. Manufacturing the new hybrid membranes is simpler than that of ceramic membranes, because the material is flexible and will not show cracks. What they have in common with ceramic membranes is the rapid flow: an advantage of this is that the membrane surface can be kept small.

The hybrid membranes are suitable for ‘drying’ solvents and biofuels, an application for which there is a large potential market worldwide. The main advantage of membrane technology is that it consumes far less energy than common distillation techniques.

The scientists also foresee opportunities in separating hydrogen gas from gas mixtures. This implies a broad range of applications in sustainable energy. Apart from that, the hybrid membranes are suitable for desalinating water. Using a hybrid membrane that is much smaller than the current polymer membranes, the same result can be achieved.

The results have been achieved in a close cooperation of scientists from the Inorganic Materials Science Group of the MESA+ Institute for Nanotechnology (UT), the Energy Efficiency in Industry department of ECN and the University of Amsterdam. The invention has been patented worldwide.

The article ‘Hybrid ceramic nanosieves: stabilizing nanopores with organic links’ by Hessel Castricum, Ashima Sah, Robert Kreiter, Dave Blank, Jaap Vente and André ten Elshof has been published in Chemical Communications (ChemComm) of the Royal Society of Chemistry in de UK.

Adapted from materials provided by University of Twente.

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New Technique Makes Tissues Transparent

Daily Science Journal (Feb. 13, 2008) — If humans had see-through skin like a jellyfish, spotting disease like cancer would be a snap: Just look, and see a tumor form or grow.

Diagram of chicken breast tissue (approximately 250 microns thick) with photo-refractive crystal to counteract the scattering of light and remove the distortion it creates in images. The lower diagram would show the clearest image. (Credit: Caltech Biophotonics Laboratory)

But humans, of course, are not remotely diaphanous. "The reason a person is not transparent is that their tissues are highly scattering," sending light waves careening through the tissue instead of straight through, as they would through the tissue of that jellyfish, explains Changhuei Yang of the California Institute of Technology.

This scattering, in addition to rendering all of us opaque, makes the detection of disease a much trickier issue, requiring a host of diagnostic tests and procedures. But not, perhaps, for much longer, thanks to a new optical trick developed by Yang, an assistant professor of electrical engineering and bioengineering, and his colleagues, that counteracts the scattering of light and removes the distortion it creates in images.

It is well known that light scattering in a material is not exactly the random and unpredictable process one might imagine. In fact, scattering is deterministic, which means that the path that a beam of light takes as it traverses a particular slice of tissue and bounces and rebounds off of individual cells, is entirely predictable; if you again bounce light through that same swath of cells, it will scatter in exactly the same way.

The process is even reversible; if the individual photons of light that scattered through the tissue could be collected and sent back through the tissue, they'd bounce back along the same path and converge at the original spot from which they were sent. "The process is similar to the scattering of billiard balls on a pool table. If you can precisely reverse the paths and velocities of the billiard balls, you can cause the billiard balls to reassemble themselves into a rack," Yang explains.

Yang, along with his colleagues at Caltech, École Polytechnique Fédérale de Lausanne in Switzerland, and MIT, exploited this phenomenon to offset the murky nature of our tissues.

Their technique, called turbidity suppression by optical phase conjugation (TSOPC), is surprisingly simple. The scientists used a holographic crystal to record the scattered light pattern emerging from a 0.46-mm-thick piece of chicken breast. They then holographically played the pattern back through the tissue section to recover the original light beam. "This is similar to grabbing hold of the direction of time flow and turning it around; the time-reversed photons must retrace their trajectories through the tissue," Yang says. "The task is formidable though, as this is comparable to starting with a rack of 10 to the 18th power billiard balls (or photons), scattering them around the table, and attempting to reassemble them into a rack."

"Until we did this study, it wasn't clear that the effect will be observable with biological tissues. We were pleasantly surprised that the effect was readily observable and remarkably robust," Yang says. "This study opens up numerous possibilities in the use of optical time reversal in biomedicine."

One possible use of the technique is in photodynamic therapy, in which a highly focused beam of light is aimed at cancerous cells that have absorbed cell-killing light-sensitive compounds. When the light hits the cells, the compounds are activated and destroy the cells. Photodynamic therapy is most effective in treating cancers on the skin surface. Yang's technique, however, offers a way to concentrate light onto cancer-killing compounds located more deeply within tissue.

Yang's idea is to inject strongly light-scattering particles that are coated with light-activated cancer-killing drugs into diseased tissue. Shine a beam of light into the tissue, and it would be reflected off the scattering compounds as it bounces through the tissue. Some of the scattered light would return to the source, where it could be recorded as a hologram.

This hologram would contain information about the path that the scattered light took through the tissue, and, in effect, describe the optimal path BACK toward the light-scattering molecule--and the cancer-killing compounds. Playing back the signal with a stronger burst of light will then activate the therapeutic drugs, which kill the cancer cells.

In addition, the technique could offer a way to power miniature implants buried deep within tissues. "If you take a quick survey of what is out there at present, you will see that implants are fairly large," Yang says. "For example, a pacemaker is about the size of a cell phone. Why are they so big? A large part of the reason is because they need to carry their own power sources."

The key to making smaller implants, then--say, the size of a pen tip--is to eliminate the power sources. "I think implants that carry photovoltaic receivers are particularly promising," he says. "The effect can be applied to tailor light-delivery mechanisms to efficiently channel light into tissues and onto these implants."

A study describing the process appears in the February issue of the journal Nature Photonics. Zahid Yaqoob, a postdoctoral fellow in electrical engineering at Caltech, performed most of the experiments reported in the paper. The other authors of the paper are Demetri Psaltis, professor of optics and dean of engineering, École Polytechnique Fédérale de Lausanne in Switzerland, and Michael S. Feld, a professor of physics at MIT.

Adapted from materials provided by California Institute of Technology.

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Biofuel Crops That Require Destroying Native Ecosystems Worsens Global Warming

Daily Science Journal (Feb. 12, 2008) — Turning native ecosystems into "farms" for biofuel crops causes major carbon emissions that worsen the global warming that biofuels are meant to mitigate, according to a new study by the University of Minnesota and the Nature Conservancy.

Aerial view of farmland in Indonesia. The conversion of peatlands for palm oil plantations in Indonesia ran up the greatest carbon debt, one that would require 423 years to pay off. (Credit: iStockphoto)

The carbon lost by converting rainforests, peatlands, savannas, or grasslands outweighs the carbon savings from biofuels. Such conversions for corn or sugarcane (ethanol), or palms or soybeans (biodiesel) release 17 to 420 times more carbon than the annual savings from replacing fossil fuels, the researchers said. The carbon, which is stored in the original plants and soil, is released as carbon dioxide, a process that may take decades. This "carbon debt" must be paid before the biofuels produced on the land can begin to lower greenhouse gas levels and ameliorate global warming.

The conversion of peatlands for palm oil plantations in Indonesia ran up the greatest carbon debt, one that would require 423 years to pay off. The next worst case was the production of soybeans in the Amazon, which would not "pay for itself" in renewable soy biodiesel for 319 years.

"We don't have proper incentives in place because landowners are rewarded for producing palm oil and other products but not rewarded for carbon management," said University of Minnesota Applied Economics professor Stephen Polasky, an author of the study. "This creates incentives for excessive land clearing and can result in large increases in carbon emissions.

"This research examines the conversion of land for biofuels and asks the question 'Is it worth it?'," said lead author Joe Fargione, a scientist for The Nature Conservancy. "And surprisingly, the answer is no."

Fargione began the work as a University of Minnesota postdoctoral researcher with Polasky, Regents Professor of Ecology David Tilman; he completed it after joining the Nature Conservancy. They, along with university researchers Jason Hill and Peter Hawthorne, also contributed to the work.

"If you're trying to mitigate global warming, it simply does not make sense to convert land for biofuels production," said Fargione. "All the biofuels we use now cause habitat destruction, either directly or indirectly. Global agriculture is already producing food for six billion people. Producing food-based biofuel, too, will require that still more land be converted to agriculture."

These findings coincide with observations that increased demand for ethanol corn crops in the United States is likely contributing to conversion of the Brazilian Amazon and Cerrado (tropical savanna). American farmers traditionally rotated corn crops with soybeans, but now they are planting corn every year to meet the ethanol demand and Brazilian farmers are planting more of the world's soybeans. And they're deforesting the Amazon to do it.

The researchers also found significant carbon debt in the conversion of grasslands in the United States and rainforests in Indonesia.

Researchers did note that some biofuels do not contribute to global warming because they do not require the conversion of native habitat. These include waste from agriculture and forest lands and native grasses and woody biomass grown on marginal lands unsuitable for crop production. The researchers urge that all fuels be fully evaluated for their impacts on global warming, including impacts on habitat conversion.

"Biofuels made on perennial crops grown on degraded land that is no longer useful for growing food crops may actually help us fight global warming," said Hill. "One example is ethanol made from diverse mixtures of native prairie plants. Minnesota is well poised in this respect."

"Creating some sort of incentive for carbon sequestration, or penalty for carbon emissions, from land use is vital if we are serious about addressing this problem," Polasky said.

"We will need to implement many approaches simultaneously to solve climate change. There is no silver bullet, but there are many silver BBs," said Fargione. "Some biofuels may be one silver BB, but only if produced without requiring additional land to be converted from native habitats to agriculture."

The work will be published in Science later this month and will be posted online Thursday, Feb. 7.

The work was supported by the University of Minesota's Initiative for Renewable Energy and the Environment and the National Science Foundation.

Adapted from materials provided by University of Minnesota.

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Using Musical Chords To Analyze And Illustrate Hydrogen Molecule's Response To Laser Pulses

Daily Science Journal (Feb. 10, 2008) — For Kansas State University physics professor Uwe Thumm, confirmation of a theory about the behavior of small molecules became music to his ears -- literally. He and colleagues in Heidelberg, Germany, have shown how a hydrogen molecule responds to laser pulses by using the changing musical chord created by the molecule's vibrational motion.

Researchers in Heidelberg visualized the development over time of molecular resonance. The distance between the two nuclei (R) in the heavy hydrogen (deuterium) ion D2+ is plotted against the time. After approximately 100 femtoseconds, the wave packet, i.e. the location of the nuclei, starts to become hazy, after 400 femtoseconds there is a "revival" and the wave packet is put back together again. (Credit: Max Planck Institute for Nuclear Physics)

Thumm is a member of K-State's J.R. Macdonald Laboratory, where he is among several researchers who work on the properties and behavior of atoms and small molecules.

For decades, researchers had used the Macdonald Laboratory to make atoms and molecules collide with particles. Thumm said much of what scientists know about atoms and molecules is based on such collision experiments. To predict and explain what happens in these collisions, a large group of experimental physicists works closely with Thumm and two other theorists. The theorists use computers, make models and crunch numbers with the hope of producing results that are compatible with what experiments show.

Thanks to improvements in laser technology, around 1999 the Macdonald Laboratory researchers realized that they could transfer a lot of their expertise in atomic collisions to study in detail what happens when atoms and molecules get irradiated by very intense laser light. The new laser systems in the laboratory offer some advantages over the big particle accelerators, Thumm said. The laser pulses offer more control and can be made so short that the researchers now routinely observe the motion of nuclei inside small molecules in time. In addition, the laser pulses' peak intensity is enormous and would equal all of the sun's light focused onto a small spot of the size of a postage stamp or smaller.

Motivated by these opportunities, Thumm and his colleagues became curious about figuring out what would happen if the smallest and simplest molecule, hydrogen, were exposed to such ultra short and intense laser pulses. Together with his postdoctoral collaborator Bernold Feuerstein, Thumm developed a model and did calculations to determine how laser pulses influence the motion of the two protons in the hydrogen molecule.

"The short answer is that the laser pulse either makes the molecules vibrate more violently or blows them apart," Thumm said. He said this wasn't surprising because in the hydrogen molecule, two protons are connected by two electrons that function like a spring. When hit with the laser pulses, the protons oscillate back and forth.

Although this model may be easy to imagine on a large scale, Thumm said particles behave differently at the quantum level. This means that determining the locations of these oscillating protons isn't easy. Thumm described determining the protons' movements after being hit with the laser like what happens if you drop a marble in a bathtub. Looking at the circular ripples of water in the center of the tub, it's pretty easy to tell where the marble was dropped in. But when those ripples bounce off the sides of the tub, the wave pattern changes shape, and it becomes harder to tell where the marble was dropped. The wave gets delocalized. Thumm said the same thing happens to the protons not in a matter of seconds, but in a matter of femtoseconds -- that's a billionth of a millionth of a second. After about 60 femtoseconds, it's impossible to tell where the protons are.

"You quickly loose track of what the distance between the two protons is," Thumm said." All you can say is that they have a certain likelihood of being at a certain distance. This is in agreement with the bathtub experiment: Seconds after the marble was dropped, you can't tell where exactly it plunged in."

But things work differently at the quantum level, and the researchers were surprised that about 600 femtoseconds after being hit with the laser, the distance between the protons again becomes well defined. "We call this a revival of the original motion of the protons," Thumm said. "It's not going to happen in the bathtub, but it happens at the quantum level."

Thumm and Feuerstein published their theoretical prediction in 2003. Thumm said that they were pleasantly surprised when experiments at the Max-Planck Institute in Heidelberg, Germany, in 2006 confirmed the revival described in their model. "The agreement between the new experiments and our model was almost perfect and exceeded our expectations," Thumm said.

Feuerstein had since moved to Heidelberg, where he and his group of researchers continued to collaborate with Thumm's group at K-State. Excited about the success of their model, they began to analyze the molecule's vibrational motion by breaking it down into its various frequencies. Each frequency being like a note in a chord, the frequencies told researchers how the protons were behaving. However, the frequency of these molecular vibrations is way above the audible range. The two researchers share an interest in music and had collaborated musically before. So when it came time to illustrate the revival, they decided the best way to do it was to scale the frequencies down to 1,000 Hertz, which is in the range at which the human ear hears best. "This way you can listen to the vibrations and hear the revival. In the same way sound is analyzed and decomposed, we decomposed the vibration with regard to the frequencies," Thumm said. Their result, a changing musical chord coupled with a movie illustrating the protons' vibrations can be heard and viewed at http://www.mpg.de/video/FilmundoAudio-KdM.wmv

Thumm said researchers hope to be able to do the same thing for more complex molecules like water or methane. Just as a C Major chord sounds different from a d minor chord, Thumm said other molecules also would have their own unique sound. Thumm and Feuerstein's most recent work was first published last fall in the Physical Review Letters. Their research was supported by the National Science Foundation, the U.S. Department of Energy and the Max-Planck Society. Thumm said such basic research supports the long-term goal of applying lasers to steer chemical reactions. The hope is to largely increase the efficiency of chemical reactions by enhancing desired reaction pathways with lasers, he said.

Adapted from materials provided by Kansas State University.

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Birds, Bats And Insects Hold Secrets For Aerospace Engineers

Daily Science Journal (Feb. 9, 2008) — Natural flyers like birds, bats and insects outperform man-made aircraft in aerobatics and efficiency. University of Michigan engineers are studying these animals as a step toward designing flapping-wing planes with wingspans smaller than a deck of playing cards.

Flapping flight is inherently unsteady, but that's why it works so well. Birds, bats and insects fly in a messy environment full of gusts traveling at speeds similar to their own. Yet they can react almost instantaneously and adapt with their flexible wings. (Credit: iStockphoto/Steve Byland)

A Blackbird jet flying nearly 2,000 miles per hour covers 32 body lengths per second. But a common pigeon flying at 50 miles per hour covers 75. The roll rate of the aerobatic A-4 Skyhawk plane is about 720 degrees per second. The roll rate of a barn swallow exceeds 5,000 degrees per second.

Select military aircraft can withstand gravitational forces of 8-10 G. Many birds routinely experience positive G-forces greater than 10 G and up to 14 G.

“Natural flyers obviously have some highly varied mechanical properties that we really have not incorporated in engineering,” said Wei Shyy, chair of the Aerospace Engineering department and an author of the new book “The Aerodynamics of Low Reynolds Number Flyers.”

“They’re not only lighter, but also have much more adaptive structures as well as capabilities of integrating aerodynamics with wing and body shapes, which change all the time,” Shyy said. “Natural flyers have outstanding capabilities to remain airborne through wind gusts, rain, and snow.” Shyy photographs birds to help him understand their aerodynamics.

Pressure generated during flight cause the flapping wings to deform, he explained. In turn, the deformed wing tells the air that the wing shape is different than it appears in still air. If appropriately handled, this phenomenon can delay stall, enhance stability and increase thrust.

Flapping flight is inherently unsteady, but that’s why it works so well. Birds, bats and insects fly in a messy environment full of gusts traveling at speeds similar to their own. Yet they can react almost instantaneously and adapt with their flexible wings.

Shyy and his colleagues have several grants from the Air Force totaling more than $1 million a year to research small flapping wing aircraft. Such aircraft would fly slower than their fixed wing counterparts, and more importantly, they would be able to hover and possibly perch in order to monitor the environment or a hostile area. Shyy’s current focus is on the aerodynamics of flexible wings related to micro air vehicles with wingspans between 1 and 3 inches.

“These days, if you want to design a flapping wing vehicle, you could build one with trial and error, but in a controlled environment with no wind gusts,” Shyy said. “We are trying to figure out how to design a vehicle that can perform a mission in an uncertain environment. When the wind blows, how do they stay on course?”

A dragonfly, Shyy says, has remarkable resilience to wind, considering how light it is. The professor chalks that up to its wing structure and flight control. But the details are still questions.

“We’re really just at the beginning of this,” Shyy said.

Shyy is the Clarence L. "Kelly" Johnson Collegiate Professor of Aerospace Engineering. Other authors of the book, “Aerodynamics of Low Reynolds Number Flyers” are: U-M research scientists Yongsheng Lian, Jian Tang and Dragos Viieru, and Hao Liu, professor of Biomechanical Engineering at Chiba University in Japan.

Other collaborators on this research include professors Luis Bernal, Carlos Cesnik and Peretz Friedmann of the University of Michigan; Hao Liu of Chiba University in Japan; Peter Ifju, Rick Lind and Larry Ukeiley of University of Florida, and Sean Humbert of University of Maryland.

Adapted from materials provided by University of Michigan.

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Knee Brace Generates Electricity From Walking

Daily Science Journal (Feb. 9, 2008) — A new energy-capturing knee brace can generate enough electricity from walking to operate a portable GPS locator, a cell phone, a motorized prosthetic joint or an implanted neurotransmitter, research involving the University of Michigan shows.

The biomechanical energy harvester includes an aluminum chassis and generator mounted on a customized orthopaedic knee brace. The device weighs 3.5 lbs. (Credit: Greg Ehlers/Simon Fraser University)

The wearable mechanism works much like regenerative braking charges a battery in some hybrid vehicles, said Arthur Kuo, an associate professor of mechanical engineering at U-M and an author of the paper.*

Regenerative brakes collect the kinetic energy that would otherwise be dissipated as heat when a car slows down. This knee brace harvests the energy lost when a human brakes the knee after swinging the leg forward to take a step.

Kuo, who called the device "a cocktail-napkin idea," says knee joints are uniquely suited for this endeavor.

"There is power to be harvested from various places in the body, and you can use that to generate electricity. The knee is probably the best place," he said. "During walking, you dissipate energy in various places, when your foot hits the ground, for example. You have to make up for this by performing work with your muscles.

"The body is clever," Kuo said. "In a lot of places where it could be dissipating energy, it may actually be storing it and getting it back elastically. Your tendons act like springs. In many places, we're not sure whether the energy is really being dissipated or you're just storing it temporarily. We believe that when you're slowing down the knee at the end of swinging the leg, most of that energy normally is just wasted."

The scientists tested the knee brace on six men walking leisurely on a treadmill at 1.5 meters per second, or 2.2 miles per hour. They measured the subjects' respiration to determine how hard they were working. A control group wore the brace with the generator disengaged to measure how the weight of the 3.5-pound brace affected the wearer.

In the mode in which the brace is only activated while the knee is braking, the subjects required less than one watt of extra metabolic power for each watt of electricity they generated. A typical hand-crank generator, for comparison, takes an average of 6.4 watts of metabolic power to generate one watt of electricity because of inefficiencies of muscles and generators.

"We've demonstrated proof of concept," Kuo said. "The prototype device is bulky and heavy, and it does affect the wearer just to carry. But the energy generation part itself has very little effect on the wearer, whether it is turned on or not. We hope to improve the device so that it is easier to carry, and to retain the energy-harvesting capabilities."

A lighter version would be helpful to hikers or soldiers who don't have easy access to electricity. And the scientists say similar mechanisms could be built into prosthetic knees other implantable devices such as pacemakers or neurotransmitters that today require a battery, and periodic surgery to replace that battery.

"A future energy harvester might be implanted along with such a device and generate its own power from walking," Kuo said.

The paper "Biomechanical Energy Harvesting: Generating Electricity During Walking with Minimal User Effort" is published in the Feb. 8 issue of the journal Science. Authors include researchers from Simon Fraser University in Canada and the University of Pittsburgh, in addition to U-M.

Adapted from materials provided by University of Michigan.

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Croatian Children Have Higher Weapons-related Death Rate During And After Homeland War

Daily Science Journal (Feb. 7, 2008) — The Homeland War in Croatia, which occurred from 1991 to 1995, led to an increase in weapon-related deaths of children during and five years after the end of the war, according to a new report.

"After World War II until the beginning of the Homeland War in 1991, most children in Croatia were not exposed to firearms and explosives in their homes or communities," the authors write as background information in the article. "Unlike many countries, personal weapon ownership was not a custom in Croatia." This changed as the Homeland War--also called the Third Balkan War--moved into Croatian land. Citizens began purchasing grenades, firearms and other weapons on the black market or taking them from military barracks after the Yugoslav army left Croatia. The population remained overly militarized in the wake of the war; in 2007, 371,684 weapons were legally owned by Croatians.

Aida Mujkic, M.D., of the University of Iowa, Iowa City, and colleagues studied Croatian children from birth through age 19 who died of weapon-related injuries between 1986 and 2005. Statistics were obtained from Croatia's national vital statistics system and included traumatic injury deaths classified by intent, including homicide, suicide and unintentional categories.

Compared with the period before the war, rates of homicide and suicide with weapons more than tripled during the war--from .22 to .73 homicides and .51 to 1.64 suicides per 100,000 children. Unintentional weapon-related deaths also increased by more than six-fold, from .25 to 1.63 per 100,000 children.

"These increases persisted for five years following the end of the war and decreased more than five years after the war," the authors write. Weapons-related deaths in the early postwar period--1996 to 2000--remained more than twice as high as before the war, and the weapon-related suicide rate remained more than three times that of the pre-war period. Homicide and unintentional injury deaths decreased significantly in the late post-war period, 2001 to 2005, and suicide rates were the same as in the pre-war period. The number of children who died from causes other than weapons did not change over the course of the study.

"Programs that focus on the prevention of weapon-related injuries should be integrated into programs that assist countries in rebuilding after political unrest," the authors conclude. "The combination of psychological effects of war on children with an increased presence of weapons may present a particularly important area for prevention."

Journal reference: Arch Pediatr Adolesc Med. 2008;162[2]:140-144.

This study was supported by an NIH grant from the University of Iowa/Fogarty International Traumatic Injury Training Program.

Adapted from materials provided by JAMA and Archives Journals.

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Magma And Volcanoes: Physicists Explain Dance Marathon Of Wispy Feature In Roiling Fluids

Daily Science Journal (Feb. 7, 2008) — Theoretical physicists at the University of Chicago are suggesting how thin spouts of magma in the Earth's mantle can persist long enough to form hotspot volcanism of the type that might have created the Hawaiian Islands.

University of Chicago physicists Wendy Zhang (left) and Laura Schmidt explain a feature of convecting fluids that colleagues have observed in laboratory experiments. The feature may help explain how hotspot volcanism created the Hawaiian Islands and other such landforms. (Credit: Dan Dry)

Their calculations also apply to tendrils only a few inches long that form in convecting fluids under laboratory conditions. University of Chicago graduate student Laura Schmidt and Wendy Zhang, an Assistant Professor in Physics, will detail their findings in the Feb. 1 issue of the journal Physical Review Letters.

The work was inspired by laboratory experiments conducted by Anne Davaille in France that mimic, in a simplified way, convecting bubbles of magma as they might look deep beneath the Earth's surface. "This is one robust feature of thermal convection," Zhang said.

"It's a useful thing to know because it's the kind of thing that happens in all sorts of different industries, in all sorts of different contexts." These include oil extraction, the chemical industry and in certain biotechnological applications.

Earth scientists also have theorized that mantle plumes form on a regional scale in the Earth's interior, sometimes breaking the surface to form small landmasses, including Hawaii and Iceland. Nevertheless, debate swirls around how, or even if, mantle plumes can account for such surface features.

Geophysicists often liken a pot of boiling water as a smaller, more rapid version of the convection that takes place in the mantle, the layer of Earth that lies between the surface crust and its core. But unlike a pot of water, the Earth's interior consists of layers with different properties.

In laboratory experiments, Anne Davaille, a geophysicist at the University of Paris 7, studies convection in a small tank by heating two layers of colored liquids of differing densities. She observed the formation and persistence of thin tendrils between the layers, which correspond to subsurface plumes measuring scores of miles across.

"It seems so thin and tenuous, how could it possibly manage to hold itself in place over time as everything else is going on around it?" Zhang asked. "Somehow, they manage to hold themselves together."

The tendrils persist for hours, even as experimental conditions change. "These tendrils have fluid flowing through them, and it starts to mix the two layers," Schmidt said. "When the two layers mix, then the viscosity of the layers changes as well."

Following a series of visits to Davaille's lab, Schmidt and Zhang sought to mathematically explain the phenomenon.

"When you look at the shape of these very thin tendrils, there's something very striking that Anne noticed right away," Zhang said. The tendrils seem to emerge from flow lines that resemble the flared-out end of a trumpet. This trumpet shape marked the location of a stagnation point. Both Davaille's experiments and Schmidt's calculations agree: The thinnest tendrils that persist have a stagnation point.

Schmidt had seen a similar stagnation point in experiments she conducted in the laboratory of Sidney Nagel, the Stein-Freiler Distinguished Service Professor in Physics at the University of Chicago. Those experiments involved unmixable fluids, such as water and oil, instead of the fresh water and salt water mixing in Davaille's laboratory.

Nevertheless, the experimental similarities provided Schmidt and Zhang insights that helped solve the problem. In previous studies, other theoreticians suggested how large flows might rise through the tendrils from the base of the hot spots, Schmidt said. She and Zhang approached the problem differently.

"We include the effect of the stagnation point," Schmidt explained. "Our tendrils are really a thin skin or thin layer of the surface between the fluids that is drawn up. It's not a bulk flow going up through the tendril."

Adapted from materials provided by University of Chicago, via EurekAlert!, a service of AAAS.

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Particle Accelerator May Reveal Shape Of Alternate Dimensions

Daily Science Journal (Feb. 6, 2008) — When the world's most powerful particle accelerator starts up later this year, exotic new particles may offer a glimpse of the existence and shapes of extra dimensions.

A new particle accelerator, the Large Hadron Collider, is scheduled to begin operating later this year near Geneva, Switzerland. (Credit: CERN)

Researchers from the University of Wisconsin-Madison and the University of California-Berkeley say that the telltale signatures left by a new class of particles could distinguish between possible shapes of the extra spatial dimensions predicted by string theory.

String theory, which describes the fundamental particles of the universe as tiny vibrating strings of energy, suggests the existence of six or seven unseen spatial dimensions in addition to the time and three space dimensions that we normally see.

Much as the shape of a musical instrument determines its sound, the shape of these dimensions determines the properties and behavior of our four-dimensional universe, says Gary Shiu, lead author of a paper appearing in the Jan. 25 issue of Physical Review Letters.

"The shape of the dimensions is crucial because, in string theory, the way the string vibrates determines the pattern of particle masses and the forces that we feel," says the UW-Madison physics professor.

Zeroing in on that shape should further our understanding and predictions of our four-dimensional world, Shiu says. "There are myriad possibilities for the shapes of the extra dimensions out there. It would be useful to know a way to distinguish one from another and perhaps use experimental data to narrow down the set of possibilities."

Such experimental evidence could appear in data from a new particle accelerator, the Large Hadron Collider, scheduled to begin operating later this year near Geneva, Switzerland.

In an accelerator, smashing atomic nuclei head-on at nearly the speed of light can briefly create new high-energy and highly unstable particles, which quickly decay into a shower of detectable lower energy ones. Characteristic patterns of decay serve as fingerprints of the fleeting exotic particles and, possibly, the shape of the unseen dimensions.

With colleagues Bret Underwood and Kathryn Zurek at UW-Madison and Devin Walker at UC-Berkeley, Shiu shows in the new study that the signature patterns from particles called Kaluza-Klein (KK) gravitons can distinguish between different proposed extra-dimensional geometries.

How" Shiu compares the effect to a darkened room in which patterns of sound resonating off the walls can reveal the shape of the room. Similarly, KK gravitons are sensitive to the extra-dimensional shape and, through their behavior and decay, may reveal clues to that shape.

The current study shows that, in simulations, even small geometric variations lead to visible differences in KK graviton signatures, Underwood says.

Based on these results, Shiu says, "At least in principle, one may be able to use experimental data to test and constrain the geometry of our universe."

Last year, Shiu and Underwood reported that clues to dimensional geometries might also be visible in patterns of cosmic radiation left over from the Big Bang. The new work complements the previous approach, they say.

"The more hints we get, the better idea we have about the underlying physics," says Shiu.

Adds Underwood, "If the cosmology and particle physics data agree, it's an indication we're on the right track."

The work was supported by the National Science Foundation, the U.S. Department of Energy, the Research Corporation, and a University of California Presidential Fellowship.

Adapted from materials provided by University of Wisconsin-Madison.

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Bio-crude Turns Cheap Waste Into Valuable Fuel

Daily Science Journal (Feb. 5, 2008) — CSIRO and Monash University have developed a chemical process that turns green waste into a stable bio-crude oil. The bio-crude oil can be used to produce high value chemicals and biofuels, including both petrol and diesel replacement fuels.

Forest waste can be converted into bio-crude oil. (Credit: Image courtesy of CSIRO Australia)

“By making changes to the chemical process, we’ve been able to create a concentrated bio-crude which is much more stable than that achieved elsewhere in the world,” says Dr Steven Loffler of CSIRO Forest Biosciences.

“This makes it practical and economical to produce bio-crude in local areas for transport to a central refinery, overcoming the high costs and greenhouse gas emissions otherwise involved in transporting bulky green wastes over long distances.”

The process uses low value waste such as forest thinnings, crop residues, waste paper and garden waste, significant amounts of which are currently dumped in landfill or burned.

“By using waste, our Furafuel technology overcomes the food versus fuel debate which surrounds biofuels generated from grains, corn and sugar,” says Dr Loffler.

“The project forms part of CSIRO’s commitment to delivering cleaner energy and reducing greenhouse gas emissions by improving technologies for converting waste biomass to transport fuels.”

The plant wastes being targeted for conversion into biofuels contain chemicals known as lignocellulose, which is increasingly favoured around the world as a raw material for the next generation of bio-ethanol.

Lignocellulose is both renewable and potentially greenhouse gas neutral. It is predominantly found in trees and is made up of cellulose; lignin, a natural plastic; and hemicellulose.

CSIRO and Monash University will apply to patent the chemical processes underpinning the conversion of green wastes to bio-crude oil once final laboratory trials are completed.

The research to date is supported by funding from CSIRO’s Energy Transformed Flagship program, Monash University, Circa Group and Forest Wood Products Australia.

National Research Flagships CSIRO initiated the National Research Flagships to provide science-based solutions in response to Australia’s major research challenges and opportunities. The nine Flagships form multidisciplinary teams with industry and the research community to deliver impact and benefits for Australia.

Adapted from materials provided by CSIRO Australia.

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Plastic Bottles Release Potentially Harmful Chemicals (Bisphenol A) After Contact With Hot Liquids

Daily Science Journal (Feb. 5, 2008) — When it comes to Bisphenol A (BPA) exposure from polycarbonate plastic bottles, it's not whether the container is new or old but the liquid's temperature that has the most impact on how much BPA is released, according to University of Cincinnati (UC) scientists.

Scott Belcher, PhD, tested polycarbonate plastic bottles like these for Bisphenol A. (Credit: Image courtesy of University of Cincinnati)

Scott Belcher, PhD, and his team found when the same new and used polycarbonate drinking bottles were exposed to boiling hot water, BPA, an environmental estrogen, was released 55 times more rapidly than before exposure to hot water.

"Previous studies have shown that if you repeatedly scrub, dish-wash and boil polycarbonate baby bottles, they release BPA. That tells us that BPA can migrate from various polycarbonate plastics," explains Belcher, UC associate professor of pharmacology and cell biophysics and corresponding study author. "But we wanted to know if 'normal' use caused increased release from something that we all use, and to identify what was the most important factor that impacts release."

"Inspired by questions from the climbing community, we went directly to tests based on how consumers use these plastic water bottles and showed that the only big difference in exposure levels revolved around liquid temperature: Bottles used for up to nine years released the same amount of BPA as new bottles."

BPA is one of many man-made chemicals classified as endocrine disruptors, which alter the function of the endocrine system by mimicking the role of the body's natural hormones. Hormones are secreted through endocrine glands and serve different functions throughout the body.

The chemical--which is widely used in products such as reusable water bottles, food can linings, water pipes and dental sealants--has been shown to affect reproduction and brain development in animal studies.

"There is a large body of scientific evidence demonstrating the harmful effects of very small amounts of BPA in laboratory and animal studies, but little clinical evidence related to humans," explains Belcher. "There is a very strong suspicion in the scientific community, however, that this chemical has harmful effects on humans."

Belcher's team analyzed used polycarbonate water bottles from a local climbing gym and purchased new bottles of the same brand from an outdoor retail supplier.

All bottles were subjected to seven days of testing designed to simulate normal usage during backpacking, mountaineering and other outdoor adventure activities.

The UC researchers found that the amount of BPA released from new and used polycarbonate drinking bottles was the same -- both in quantity and speed of release -- into cool or temperate water.

However, drastically higher levels of BPA were released once the bottles were briefly exposed to boiling water.

"Compared to the rate of release from the same bottle, the speed of release was 15 to 55 times faster," explains Belcher.

Prior to boiling water exposure, the rate of release from individual bottles ranged from 0.2 to 0.8 nanograms per hour. After exposure, rates increased to 8 to 32 nanograms per hour.

Belcher stresses that it is still unclear what level of BPA is harmful to humans. He urges consumers to think about how cumulative environmental exposures might harm their health.

"BPA is just one of many estrogen-like chemicals people are exposed to, and scientists are still trying to figure out how these endocrine disruptors--including natural phyto-estrogens from soy which are often considered healthy--collectively impact human health," he says. "But a growing body of scientific evidence suggests it might be at the cost of your health."

The UC team reports its findings in the Jan. 30, 2008 issue of the journal Toxicology Letters. UC graduate student Hoa Le and summer undergraduate research fellows Emily Carlson and Jason Chua also participated in this study, which was funded by a National Institute of Environmental Health Sciences grant.

Adapted from materials provided by University of Cincinnati.

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DNA Is Blueprint, Contractor And Construction Worker For New Structures

Daily Science Journal (Feb. 4, 2008) — DNA is the blueprint of all life, giving instruction and function to organisms ranging from simple one-celled bacteria to complex human beings. Now Northwestern University researchers report they have used DNA as the blueprint, contractor and construction worker to build a three-dimensional structure out of gold, a lifeless material.

Computer rendition of a structure created by using DNA to assemble nanoparticles into well-defined crystal lattices. (Credit: Northwestern University)

Using just one kind of nanoparticle (gold) the researchers built two common but very different crystalline structures by merely changing one thing -- the strands of synthesized DNA attached to the tiny gold spheres. A different DNA sequence in the strand resulted in the formation of a different crystal.

The technique, to be published in the journal Nature, and reflecting more than a decade of work, is a major and fundamental step toward building functional "designer" materials using programmable self-assembly. This "bottom-up" approach will allow scientists to take inorganic materials and build structures with specific properties for a given application, such as therapeutics, biodiagnostics, optics, electronics or catalysis

Most gems, such as diamonds, rubies and sapphires, are crystalline inorganic materials. Within each crystal structure, the atoms have precise locations, which give each material its unique properties. Diamond's renowned hardness and refractive properties are due to its structure -- the precise location of its carbon atoms.

In the Northwestern study, gold nanoparticles take the place of atoms. The novel part of the work is that the researchers use DNA to drive the assembly of the crystal. Changing the DNA strand's sequence of As, Ts, Gs and Cs changes the blueprint, and thus the shape, of the crystalline structure. The two crystals reported in Nature, both made of gold, have different properties because the particles are arranged differently.

"We are now closer to the dream of learning, as nanoscientists, how to break everything down into fundamental building blocks, which for us are nanoparticles, and reassembling them into whatever structure we want that gives us the properties needed for certain applications," said Chad A. Mirkin, one of the paper's senior authors and George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, professor of medicine and professor of materials science and engineering. In addition to Mirkin, George C. Schatz, Morrison Professor of Chemistry, directed the work.

By changing the type of DNA on the surface of the particles, the Northwestern team can get the particles to arrange differently in space. The structures that finally form are the ones that maximize DNA hybridization. DNA is the stabilizing force, the glue that holds the structure together. "These structures are a new form of matter," said Mirkin, "that would be difficult, if not impossible, to make any other way."

He likens the process to building a house. Starting with basic materials such as bricks, wood, siding, stone and shingles, a construction team can build many different types of houses out of the same building blocks. In the Northwestern work, the DNA controls where the building blocks (the gold nanoparticles) are positioned in the final crystal structure, arranging the particles in a functional way. The DNA does all the heavy lifting so the researchers don't have to.

Mirkin, Schatz and their team just used one building block, gold spheres, but as the method is further developed, a multitude of building blocks of different sizes can be used -- with different composition (gold, silver and fluorescent particles, for example) and different shapes (spheres, rods, cubes and triangles). Controlling the distance between the nanoparticles is also key to the structure's function.

"Once you get good at this you can build anything you want," said Mirkin, director of Northwestern's International Institute for Nanotechnology.

"The rules that govern self-assembly are not known, however," said Schatz, "and determining how to combine nanoparticles into interesting structures is one of the big challenges of the field."

The Northwestern researchers started with gold nanoparticles (15 nanometers in diameter) and attached double-stranded DNA to each particle with one of the strands significantly longer than the other. The single-stranded portion of this DNA serves as the "linker DNA," which seeks out a complementary single strand of DNA attached to another gold nanoparticle. The binding of the two single strands of linker DNA to each other completes the double helix, tightly binding the particles to each other.

Each gold nanoparticle has multiple strands of DNA attached to its surface so the nanoparticle is binding in many directions, resulting in a three-dimensional structure -- a crystal. One sequence of linker DNA, programmed by the researchers, results in one type of crystal structure while a different sequence of linker DNA results in a different structure.

"We even found a case where the same linker could give different structures, depending on the temperatures at which the particles were mixed," said Schatz.

Using the extremely brilliant X-rays produced by the Advanced Photon Source synchrotron at Argonne National Laboratory in combination with computational simulations, the research team imaged the crystals to determine the exact location of the particles throughout the structure. The final crystals have approximately 1 million nanoparticles.

"It took scientists decades of work to learn how to synthesize DNA," said Mirkin. "Now we've learned how to use the synthesized form outside the body to arrange lifeless matter into things that are useful, which is really quite spectacular."

The Nature paper, entitled "DNA-programmable nanoparticle crystallization" is to be published January 31, 2008. In addition to Mirkin and Schatz, other authors are Sung Yong Park, a former postdoctoral fellow in Schatz's lab and now at the University of Rochester (lead author); graduate student Abigail K. R. Lytton-Jean, Northwestern University; Byeongdu Lee, Advanced Photon Source, Argonne National Laboratory; and Steven Weigand, Northwestern's DND-CAT Synchrotron Research Center at Argonne's Advanced Photon Source.

Adapted from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.

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New Nanotube Findings Give Boost To Potential Biomedical Applications

Daily Science Journal (Feb. 4, 2008) — Carbon nanotubes-cylinders so tiny that it takes 50,000 lying side by side to equal the width of a human hair-are packed with the potential to be highly accurate vehicles for administering medicines and other therapeutic agents to patients. But a dearth of data about what happens to the tubes after they discharge their medical payloads has been a major stumbling block to progress.

A representation of a carbon nanotube accessorized with a coating of branched PEG. (Credit: Courtesy of Hongjie Dai)

Now, Stanford researchers, who spent months tracking the tiny tubes inside mice, have found some answers.

Studies in mice already had shown that most nanomaterials tend to accumulate in organs such as the liver and spleen, which was a concern because no one knew how long they could linger. But fears that the tiny tubes might be piling up in vital organs, like discarded refrigerators at the bottom of a rural ravine, can now be put to rest, said Hongjie Dai, the J. G. Jackson and C. J. Wood Professor of Chemistry at Stanford, whose research team has demonstrated that the nanotubes exit the organs.

Dai and his group found that the carbon nanotubes leave the body primarily through the feces, with some by way of the urine. ''That's nice to know,'' Dai said. ''This now proves that they do get out of the system.''

The full extent of the news, which is scheduled to be published the week of Jan. 28 in Proceedings of the National Academy of Sciences Online Early Edition (PNAS), is even better than that: The three-month-long study also allays worries that the nanotubes, by simply remaining in the organs for a long time, would prove toxic to the mouse.

''None of the mice died or showed any anomaly in the blood chemistry or in the main organs,'' said Dai, senior author on the PNAS paper. ''They appear very healthy, and they are gaining weight, just like normal mice. There's no obvious toxicity observed.'' The lack of toxicity of nanotubes in mice is consistent with a previous pilot study done by Sanjiv Gambhir, a professor of radiology at Stanford, and his research group in collaboration with Dai's group.

''This is the first time anyone has done a systematic circulation and excretion study like this for nanotubes, and data on other nano particles is also scarce,'' Dai said. ''The excretion pathway may apply to other nano materials and may need to be looked at closely like this also.''

Previous research published by Dai's group has demonstrated the potential for using nanotubes in treating cancerous cells and targeting tumors in mice.

His group used Raman spectroscopy, a method of applying light from a laser beam that effectively ''illuminates'' the presence of the target molecules in the organs of the mice.

Being hit with light from the beam causes a detectable change in the state of a molecule's energy. Carbon nanotubes, composed entirely of carbon atoms that are mostly arranged in linked hexagonal rings, give off a strong signal in response to the beam. This allowed the researchers to pinpoint the position of the chosen molecules, as well as ascertain their abundance in the blood or organs.

Previous detection methods that relied on attaching fluorescent labels or spectroscopic tags to the nanotubes had yielded unreliable results. The attachments tended to either come loose from the tubes or decay over time spans ranging from a few days to only a few hours-far too short to reveal the ultimate fate of the nanotubes.

While knowing the carbon nanotubes will move through the digestive system at a healthy pace is critical to future practical applications, it is also crucial that the nanotubes not enter the digestive system too soon after being injected; they need to spend enough time in the circulatory system to find their way to their target location.

The key to fine-tuning the carbon nanotubes' speed of circulation turns on how the basic, bare-bones floor model is chemically accessorized.

''You can make the nanotubes circulate a very long time in the blood, if the chemistry is done right,'' Dai said. The researchers found that coating their carbon nanotubes with polyethylene glycol (PEG), a common ingredient in cosmetics, worked best.

They used a form of PEG with three little limbs sprouting off a central trunk. ''Those provide better shielding to the nanotube than just a single branch. Therefore, they interact less with the biological molecules around them,'' Dai said.

The team stuffed the PEG liberally into the linked hexagonal rings that compose the nanotubes, prompting Dai to describe the end result as resembling rolled-up chicken wire with feathers sticking out all over.

Though they may sound less than gorgeous visually, the feathery nanotubes turned in a beautiful performance in practical terms, Dai said. The coating of PEG made the nanotubes highly water soluble, which helped them to stay in the blood instead of being absorbed.

''They circulate in the blood for about 10 hours or so in mice, which seems to be a good length of time,'' Dai said.

The right chemical coating on nanotubes also can help ease them out of the mouse in a timely fashion, and the three-branched PEG was effective there, too.

Dai's earlier research demonstrated that nanotubes have promise for treating cancer with two different approaches. Once they have zeroed in on the target cells, shining light on the nanotubes causes them to generate heat, which can kill cancer cells. The other method is to rig the nanotubes to accumulate at targeted sites, where they can deliver medication from within the tubes.

''[Carbon nanotubes] seem to be promising for biomedical applications and for potentially treating cancer, either using drugs or using the physical properties,'' Dai said. ''This is the reason we carried out the study of the fate of nanotubes in mice. I think this is really a very fundamental issue.''

The research was funded by the Cancer Center for Nanotechnology Excellence, which is funded by the National Institutes of Health and the National Cancer Institute. The first author of the PNAS paper is Zhuang Liu, graduate student in chemistry. The paper's other authors, all affiliated with Stanford University, are Xiaoyuan ''Shawn'' Chen, assistant professor in radiology; Dr. Corrine Davis of the Veterinary Service Center in the Department of Comparative Medicine; Weibo Cai, postdoctoral scholar in radiology; and Lina He, formerly a technician in Chen's research group.

Adapted from materials provided by Stanford University.

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Finding New Oil In Long-exhausted Oil Wells

Daily Science Journal (Feb. 3, 2008) — Under contemporary conditions, it is more economically sound not to look for new oil fields but to overhaul old ones. Oil reappears from time to time in old deposits and long ago exhausted oil wells.

The earth's crust is similar to a sandwich cake, consisting of hard layers and fractured-porous layers saturated by various fluids, including oil. In some places, the crust is penetrated by an extremely dense network of fissures and ruptures. Ruptures form cavities located almost horizontally and united into a network. All this complicated system is in constant motion due to tectonic forces’ action. The layers are moving, fissures are widening and acting as a rubber bulb: liquid starts coming into formed interstice from surrounding porous layers. In case of significant tectonic tensions, liquid moves at large distances.

This phenomenon attracts attention of multiple researchers. Specialists of the Institute of Oil and Gas Problems under the guidance of Academician Dmitrievsky offer their explanation.

According to the researchers’ opinion, this mechanism of liquid movement in the crust is the most intense and universal among all possible ones. It acts both in ruptures and in thin fractured layers, which stretch at significant distances. Vibrations in the crust drive fluids along all possible directions, including horizontal and even downward directions. Migration occurs along lengthy cavities and fractures systems, located at the depth of 10 to 15 kilometers.

Liquid movement caused by widening of internal cavities is of vibrating character. Oil sometimes rushes in or sometimes floods back. The mode and period of vibration depend on the size of perturbed area. In large porous layers, the vibration period makes about 10 thousand years. In the ruptures, the period is shorter and it varies from a thousand to hundreds and even dozens of years, if rupture zones are located at small depths.

The researchers have investigated the carbohydrates migration process from the petroliferous stratum into the upper layers in several regions. An example can be the Romashinskoye oilfield in Tatarstan. The volume of produced oil there has significantly exceeded the previously asserted reserves. According to the TATANEFT Joint Stock Company’s data, more than 65% of oil in Tatarstan is produced in old oilfields exhausted by 80%. However, supplementary exploration of the known deposits allowed to increment reserves of oil by one and a half times within the last 25 years. In the Romashinskoye oilfield, the researchers also discovered old exhausted drillings with regenerated inflow of oil and oil with water.

The space of oil pools and their reserves increase with increasing rupture network density. It is interesting to note that the depth of sedimentary covering in the zone of the gigantic Romashinskoye oilfield does not exceed 2 kilometers on average, and this mantle does not possess significant oil potential. Most likely, oil cames to these locations from the direction of Pre-Ural downfold.

In the researchers’ opinion, to overhaul old oil deposits is currently much more profitable and efficient than expensive geological exploration works at new locations.

Adapted from materials provided by Informscience.

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Swarm Approach To Photography Improves Contrast And Detail In Digital Photos

Daily Science Journal (Feb. 3, 2008) — A new approach to cleaning up digital photos and other images has been developed by researchers in the UK and Jordan. The method uses a computer algorithm known as a PSO (Particle Swarm Optimization) to intelligently boost contrast and detail in an image without distorting the underlying features.

Malik Braik and Alaa Sheta of the Department of Information Technology, at Al-Balqa Applied University, in Salt, Jordan, working with Aladdin Ayesh in the Division of Computer Engineering, at De Montfort University, Leicester, UK, explain that the Particle Swarm Optimization (PSO) algorithm represents an entirely new approach to solving all kinds of optimization problems. PSO has recently been used in computer science and electrical engineering.

The roots of the PSO algorithms lie in Swarm Intelligence paradigm which is inspired by models of living systems, artificial life (A-life) in general, and by theories of how and why birds flock, why schools of fish behave the way they do and in particular what controls swarming insects. Despite its potential it relies on only simple mathematics and does not need powerful computers to run, which means software applications based on PSO would not be limited only to academic researchers and those with access to supercomputers.

There have been several approaches to image enhancement developed by image manipulation software companies and others. However, none comes up to the standards of the kind of image enhancement often seen in fiction, where a blurry distorted image on a screen is rendered pin-sharp at the click of a mouse. PSO, however, takes image enhancement a step closer to this ideal.

PSO is based on a mathematical model of the social interactions of swarms. The algorithm treats each version of an image as an individual member of the swarm and makes a single, small adjustment to contrast levels, edge sharpness, and other image parameters. The algorithm then determines whether the new members of the swarm are better or worse than the original according to an objective fitness criterion.

"The objective of the algorithm is to maximize the total number of pixels in the edges, thus being able to visualize more details in the images," explain the researchers. Such enhancement might be useful in improving snapshots of CCTV quality for identification of individuals or vehicle number plates, it might also have application in improving images produced with lower quality cameras, such as camera phones, that are required for use in publishing or TV where image quality standards are usually higher.

The process of enhancing step by step is repeated to create a swarm of images in computer memory which have been graded relative to each other, the fittest end up at the front of the swarm until a single individual that is the most effectively enhanced.

"The obtained results using grey scale images indicate that PSO is better than other approaches in terms of the computational time and both the objective evaluation and maximization of the number of pixels in the edges of the tested images," they add.

This research was published recently in Inderscience's International Journal of Innovative Computing and Applications.

Adapted from materials provided by Inderscience Publishers, via EurekAlert!, a service of AAAS.

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New Polymer Could Improve Semiconductor Manufacturing, Packaging

Daily Science Journal (Feb. 2, 2008) — Researchers at Rensselaer Polytechnic Institute and Polyset Company have developed a new inexpensive, quick-drying polymer that could lead to dramatic cost savings and efficiency gains in semiconductor manufacturing and computer chip packaging.

Researchers from Rensselaer Polytechnic Institute's Department of Physics and Center for Integrated Electronics have developed a new inexpensive, quick-drying polymer that could lead to dramatic cost savings and efficiency gains in semiconductor manufacturing and computer chip packaging. In this series of scanning electron microscope images of the new PES polymer in a UV-imprint lithography application, the well-defined pattern indicates the material’s potential for use in next-generation chip making techniques. (Credit: Rensselaer Polytechnic Institute)

Along with allowing enhanced performance and cost savings for conventional photolithography processes, the new material, called polyset epoxy siloxane (PES), should also enable a new generation of lower-cost, on-chip nanoimprinting lithography technology, according to the researchers.

"With this new material, chip manufacturers will be able to trim several steps from their production and packaging processes, and in turn realize a cost savings," said Toh-Ming Lu, the R.P. Baker Distinguished Professor of Physics at Rensselaer, who oversaw the study. "PES is cheaper and more reliable."

The widely adopted technique of photolithography involves using a mix of light and chemicals to generate intricate micro- and nano-scale patterns on tiny areas of silicon. As part of the process, a thin polymer film -- called a redistribution layer, and crucial to the effectiveness of device -- is deposited onto the silicon wafer, in order to ease the signal propagation delay and to protect the chip from different environmental and mechanical factors.

The new PES material developed by Lu's group and Polyset Company is one such thin polymer film, and it offers several advantages over the incumbent materials typically used in the semiconductor manufacturing industry. In addition, their new PES material can also be used as a thin polymer film for ultraviolet (UV) on-chip nanoimprinting lithography technology, which is still in the early phases of development. The consistency of using PES in conventional technology, and then continuing to use PES while academia and industry test and gradually migrate to the next generation of devices, should help ease the transition, Lu said.

"Having the ability to use one material -- our new PES -- for both photolithography and imprint will be very attractive to manufacturers," Lu said. "At its core, our project is basic research, but it also has important industry implications. It's very exciting."

Manufacturers today typically use benzocyclobutene and polyimide as polymers for redistribution layers, because of their low water absorption, thermal stability, low curing temperature, low thermal expansion, low dielectric constant, and low leakage current. Lu said PES offers significant advantages to these materials, particularly in the areas of cure temperature and water uptake.

PES cures, or dries and hardens, at 165 degrees Celsius, about 35 percent cooler than the other two materials. The need for less heat should translate directly into lower overhead costs for manufacturers, Lu said. Another advantage of PES is its low water uptake rate of less than 0.2 percent, less than the other materials. Additionally, PES adheres well to copper and can easily be made less brittle if needed. All of these attributes make PES a promising candidate for redistribution layer application and UV imprint lithography.

"The results demonstrate that PES is feasible to be used as UV-curable resist for both the redistribution application for electronic packaging and micro/nano imprint lithography," said Rensselaer Research Associate Pei-I Wang, co-author of the new paper, published recently in the Journal of Vacuum Science and Technology B.

Along with photolithography and on-chip nanoimprinting lithography, PES holds the potential for applications in other optical devices, flat-panel display, biotechnology devices, and microelectromechanical systems, Wang said.

In addition to Lu and Wang, co-authors on the paper include Rensselaer materials science and engineering professor Omkaram Nalamasu, who is also chief technical officer of Applied Materials Inc. in Santa Clara, Calif.; Rajat Ghoshal and Ram Ghoshal of Polyset Co. Inc. in Mechanicville, N.Y.; Charles Schaper of Transfer Devices Inc. in Santa Clara, Calif.; and Andrew Li of Applied Materials.

The project was funded through the New York State Foundation for Science, Technology and Innovation.

Adapted from materials provided by Rensselaer Polytechnic Institute.

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New Method For Creating Self-Assembling, Nanoscale Materials

Daily Science Journal (Feb. 2, 2008) — While biomedical, electronics, and other branches of research are marching steadily into the realm of the smaller-than-small nanometer scale, building needed materials at this scale has been problematic.

Recently, however, a team from The Scripps Research Institute unveiled a novel approach to the problem that yields a material with novel properties, which some might find reminiscent of Flubber. The material is produced using naturally occurring proteins as templates for uniform, self-assembled, nano-scale construction.

The material, an organic polymer described in today's early, online edition of the Proceedings of the National Academy of Sciences (PNAS), could one day find application in everything from screening for disease to microelectronics.

Using Nature's Tricks

Nature is replete with examples of molecules such as DNA that self-assemble with uniform patterns on the nanoscale, but until now researchers have had limited success duplicating such processes. The new study, however, provides one synthetic method that has effectively mimicked the templating strategy used in nature for nanoscale construction in the lab.

To create the new material, the Scripps Research team, led by Scripps Research President Richard Lerner and Assistant Professor Tobin Dickerson, began with a natural nanoscale product, a bacterial virus or phage. A nanometer is one billionth of a meter, or the width of a few average atoms.

Specifically, the product the team worked with was a phage known as M13. If scaled up, the phage is proportionally equivalent to a 4-foot-long pencil, with the tip and eraser roughly representing the active parts of the phage that infect bacteria. Other proteins that are biologically inert and analogous to the wood body of the pencil provide the filamentous phage's structure.

Having worked with phage extensively in other applications, the team decided to explore the possibility of using those structural proteins as a potential template for nanoscale construction. To do so, the team chemically modified molecular protrusions on the proteins so they would attract and bind with the components needed to form strands of polyacrylamide, a common polymer used to make laboratory gels.

The resulting polymer-phage combination, which twists into helices like DNA and RNA molecules, takes on the shape of a comb with the polymers as the teeth. These teeth in turn interlock to form a strangely resilient, rubbery solid.

Shocking Flexibility

Once the new material, known as a protein-polymer bioconjugate, was created, the group was shocked to find that it was almost impossible to break a sample apart. It could be sliced, but no matter how hard researchers compressed or squeezed it, it always bounced back to its original state, because the stable phage proteins act like rebar in concrete to provide strength.

Further analyses uncovered additional important characteristics. The combs do not grow completely uniformly—some combs grow more teeth than others, for instance, before interlocking with a nearby comb. But the combs can only be a prescribed distance apart for the chemical interlocking to occur, which leads to uniform size for the pores between the comb teeth. The pores proved to be about 4 nanometers wide and greater than 1 micrometer (one millionth of a meter) in length.

This uniformity is in stark contrast with experiments which showed that simply mixing the phages with polymers without the templating procedure produces a chaotic hodge podge at the molecular level.

Interestingly, after creating the material, the group discovered that a British scientist had done theoretical calculations about how flexible rods—like the phages—would pack together using the least amount of energy.

"It was extremely gratifying to see that the mathematics had exactly predicted what we were observing," says Dickerson

Putting It to Use

Although the work was intended mainly as a proof of concept for using the phages as templates, the researchers have a number of potential applications in mind. The phage can be produced easily and cheaply in very large quantities, and the polymer components are readily available and simple to combine to create the final material. These characteristics would make commercial application possible.

"In essence, bacteriophage-derived materials are a renewable resource," says Dickerson.

The defined channels established by the pores in the material might be adapted as pathways for electrons for use in microelectronics. Or, the pores might be used as a filter for certain molecules, for example to test blood samples for proteins whose presence is tied to particular diseases. More complex potential uses might include altering the biologically active portions of the phage to attract specific molecules, forcing them into the polymers' pores, or to block others.

"These tools can be visualized like Tinkertoys ® or Legos ®," says Dickerson of the possibilities. "You can think about this really in engineering terms using macroscopic analogs such as baskets, or lids, or holes."

To add to the list of potential applications, the team has already begun exploring additional materials that might be created using the basic phage construction scheme.

In addition to Dickerson and Lerner, authors on the paper, entitled "Biologically templated organic polymers with nanoscale order," were Bert Willis, Lisa Eubanks, Malcolm Wood, and Kim Janda, all of Scripps Research. See http://www.pnas.org/cgi/content/abstract/0711308105v1.

The work was supported by the Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine, and a National Institutes of Health Kirschstein National Research Service Award.

Adapted from materials provided by Scripps Research Institute.

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