Labslink Research News

MIT moves toward greener chemistry

Sat, 04 Sep 2010 04:19:23 PDT

Phosphorus, a mineral element found in rocks and bone, is a critical ingredient in fertilizers, pesticides, detergents and other industrial and household chemicals. Once phosphorus is mined from rocks, getting it into these products is hazardous and expensive, and chemists have been trying to streamline the process for decades. MIT chemistry professor Christopher Cummins and one of his graduate students, Daniel Tofan, have developed a new way to attach phosphorus to organic compounds by first splitting the phosphorus with ultraviolet light. Their method, described in the Aug. 26 online edition of Angewandte Chemie, eliminates the need for chlorine, which is usually required for such reactions and poses health risks to workers handling the chemicals. While the new reaction cannot produce the quantities needed for large-scale production of phosphorus compounds, it opens the door to a new field of research that could lead to such industrial applications, says Bertrand, who was not involved in the research. Extracting phosphorus Most natural phosphorus deposits come from fossilized animal skeletons, which are especially abundant in dried-up seabeds. Those phosphorus deposits exist as phosphate rock, which usually includes impurities such as calcium and other metals that must be removed. Purifying the rock produces white phosphorus, a molecule containing four phosphorus atoms. White phosphorous is tetrahedral, meaning it resembles a four-cornered pyramid in which each corner atom is bound to the other three. Known as P4, white phosphorus is the most stable form of molecular phosphorus. (There are also several polymeric forms, the most common of which are black and red phosphorus, which consist of long chains of broken phosphorus tetrahedrons.) For most industrial uses, phosphorus has to be attached one atom at a time, so single atoms must be detached from the P4 molecule. This is usually done in two steps. First, three of the atoms in P4 are replaced with chlorine, resulting in PCl3 — a phosphorus atom bound to three chlorine atoms. Those chlorine atoms are then displaced by organic (carbon-containing) molecules, creating a wide variety of organophosphorus compounds such as those found in pesticides. However, this procedure is both wasteful and dangerous — chlorine gas was used as a chemical weapon during World War I — so chemists have been trying to find new ways to bind phosphorus to organic compounds without using chlorine. A new reaction Cummins has long been fascinated with phosphorus, in part because of its unusual tetrahedral P4 formation. Phosphorus is in the same column of the periodic table as nitrogen, whose most stable form is N2, so chemists expected that phosphorus might form a stable P2 structure. However, that is not the case. For the past few years, Cummins' research group has been looking for ways to break P4 into P2 in hopes of attaching the smaller phosphorus molecule to organic compounds. In the new study, Cummins drew inspiration from a long overlooked paper, published in 1937, which demonstrated that P4 could be broken into two molecules of P2 with ultraviolet light. In that older study, P2 then polymerized into red posphorus. Cummins decided to see what would happen if he broke apart P4 with UV light in the presence of organic molecules that have an unsaturated carbon-carbon bond (meaning those carbon atoms are able to grab onto other atoms and form new bonds). After 12 hours of UV exposure, he found that a compound called a tetra-organo diphosphane had formed, which includes two atoms of phosphorus attached to two molecules of the organic compound. This suggests, but does not conclusively prove, that P2 forms and then immediately bonds to the organic molecule. In future studies, Cummins hopes to directly observe the P2 molecule, if it is indeed present. Cummins also plans to investigate what other organophosphorus compounds can be synthesized with ultraviolet light, including metallic compounds. He has already created a nickel-containing organophosphorus molecule, which could have applications in electronics.

Transition metal catalysts could be key to origin of life, scientists report

Sat, 04 Sep 2010 04:14:40 PDT

One of the big, unsolved problems in explaining how life arose on Earth is a chicken-and-egg paradox: How could the basic biochemicals—such as amino acids and nucleotides—have arisen before the biological catalysts (proteins or ribozymes) existed to carry out their formation? In a paper appearing in the current issue of The Biological Bulletin, scientists propose that a third type of catalyst could have jumpstarted metabolism and life itself, deep in hydrothermal ocean vents. According to the scientists' model, which is experimentally testable, molecular structures involving transition metal elements (iron, copper, nickel, etc.) and ligands (small organic molecules) could have catalyzed the synthesis of basic biochemicals (monomers) that acted as building blocks for more complex molecules, leading ultimately to the origin of life. The model has been put forth by Harold Morowitz of George Mason University (GMU), Vijayasarathy Srinivasan of GMU, and Eric Smith of the Santa Fe Institute. "There has been a big problem in the origin of life (theory) for the last 50 years in that you need large protein molecules to be catalysts to make monomers, but you need monomers to make the catalysts," Morowitz says. However, he suggests, "You can start out with these small metal-ligand catalysts, and they'll build up the monomers that can be used to make the (large protein catalysts)." A transition metal atom can act as the core of a metal-ligand complex, in which it is bound to and surrounded by other ligands. Morowitz and his colleagues propose that simple transition metal-ligand complexes in hydrothermal ocean vents catalyzed reactions that gave rise to more complex molecules. These increasingly complex molecules then acted as ligands in increasingly efficient transition metal-ligand complex catalysts. Gradually, the basic molecular ingredients of metabolism accumulated and were able to self-organize into networks of chemical reactions that laid the foundation for life. "We used to think if we could understand what carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur were doing, we would immediately be able to understand biology," Morowitz says, listing elements that constitute a large proportion of Earth's biomass. "But now we're finding that these other fairly rare elements, transition metals, are necessary in biology, so we ask, 'What was their role in the origin of life?'" The proposal suggests that the rise of life forms is a natural consequence of the unique properties of transition metals and ligand field theory, which describes the characteristics of ligand complexes. "The idea has emerged from a study of the periodic table. We strongly feel that unless you're able to see how life comes about in some formal chemical way, you're never really going to solve the problem," Morowitz says. Morowitz and his colleagues are preparing experiments to test the catalytic properties of transition metal-ligand complexes built with different types of ligands. Ligands known to bind tightly to transition metals include molecules produced during the course of the reductive citric acid cycle, a series of biochemical reactions essential for many microorganisms. "We think life probably began with the reductive citric acid cycle, and there is evidence that under hydrothermal vent conditions some of the cycle's intermediates form," Morowitz says. "We are going to start with these molecules and mix them with various transition metals, cook them at different temperatures for a while, and see what kinds of catalysts we've made." Such experiments could reveal what kinds of catalytic reactions took place to lay the foundations for life. The hypothesis also allows for the possibility that life could have arisen more than once. "Life could have originated multiples times, and, if we find life elsewhere in the universe, it could be very similar to the life we know here because it will be based on the same transition metals and ligands," Morowitz says. "It's a conjecture at the moment, but it could become a formal scientific core for the emergence of life."

Silicon oxide circuits break barrier

Wed, 01 Sep 2010 03:23:12 PDT

Rice University scientists have created the first two-terminal memory chips that use only silicon, one of the most common substances on the planet, in a way that should be easily adaptable to nanoelectronic manufacturing techniques and promises to extend the limits of miniaturization subject to Moore's Law. Last year, researchers in the lab of Rice Professor James Tour showed how electrical current could repeatedly break and reconnect 10-nanometer strips of graphite, a form of carbon, to create a robust, reliable memory "bit." At the time, they didn't fully understand why it worked so well. Now, they do. A new collaboration by the Rice labs of professors Tour, Douglas Natelson and Lin Zhong proved the circuit doesn't need the carbon at all. Jun Yao, a graduate student in Tour's lab and primary author of the paper to appear in the online edition of Nano Letters, confirmed his breakthrough idea when he sandwiched a layer of silicon oxide, an insulator, between semiconducting sheets of polycrystalline silicon that served as the top and bottom electrodes. Applying a charge to the electrodes created a conductive pathway by stripping oxygen atoms from the silicon oxide and forming a chain of nano-sized silicon crystals. Once formed, the chain can be repeatedly broken and reconnected by applying a pulse of varying voltage. The nanocrystal wires are as small as 5 nanometers (billionths of a meter) wide, far smaller than circuitry in even the most advanced computers and electronic devices. "The beauty of it is its simplicity," said Tour, Rice's T.T. and W.F. Chao Chair in Chemistry as well as a professor of mechanical engineering and materials science and of computer science. That, he said, will be key to the technology's scalability. Silicon oxide switches or memory locations require only two terminals, not three (as in flash memory), because the physical process doesn't require the device to hold a charge. It also means layers of silicon-oxide memory can be stacked in tiny but capacious three-dimensional arrays. "I've been told by industry that if you're not in the 3-D memory business in four years, you're not going to be in the memory business. This is perfectly suited for that," Tour said. Silicon-oxide memories are compatible with conventional transistor manufacturing technology, said Tour, who recently attended a workshop by the National Science Foundation and IBM on breaking the barriers to Moore's Law, which states the number of devices on a circuit doubles every 18 to 24 months. "Manufacturers feel they can get pathways down to 10 nanometers. Flash memory is going to hit a brick wall at about 20 nanometers. But how do we get beyond that? Well, our technique is perfectly suited for sub-10-nanometer circuits," he said. Austin tech design company PrivaTran is already bench testing a silicon-oxide chip with 1,000 memory elements built in collaboration with the Tour lab. "We're real excited about where the data is going here," said PrivaTran CEO Glenn Mortland, who is using the technology in several projects supported by the Army Research Office, National Science Foundation, Air Force Office of Scientific Research, and the Navy Space and Naval Warfare Systems Command Small Business Innovation Research (SBIR) and Small Business Technology Transfer programs. "Our original customer funding was geared toward more high-density memories," Mortland said. "That's where most of the paying customers see this going. I think, along the way, there will be side applications in various nonvolatile configurations." Yao had a hard time convincing his colleagues that silicon oxide alone could make a circuit. "Other group members didn't believe him," said Tour, who added that nobody recognized silicon oxide's potential, even though it's "the most-studied material in human history." "Most people, when they saw this effect, would say, 'Oh, we had silicon-oxide breakdown,' and they throw it out," he said. "It was just sitting there waiting to be exploited." In other words, what used to be a bug turned out to be a feature. Yao went to the mat for his idea. He first substituted a variety of materials for graphite and found none of them changed the circuit's performance. Then he dropped the carbon and metal entirely and sandwiched silicon oxide between silicon terminals. It worked. "It was a really difficult time for me, because people didn't believe it," Yao said. Finally, as a proof of concept, he cut a carbon nanotube to localize the switching site, sliced out a very thin piece of silicon oxide by focused ion beam and identified a nanoscale silicon pathway under a transmission electron microscope. "This is research," Yao said. "If you do something and everyone nods their heads, then it's probably not that big. But if you do something and everyone shakes their heads, then you prove it, it could be big. "It doesn't matter how many people don't believe it. What matters is whether it's true or not." Silicon-oxide circuits carry all the benefits of the previously reported graphite device. They feature high on-off ratios, excellent endurance and fast switching (below 100 nanoseconds). They will also be resistant to radiation, which should make them suitable for military and NASA applications. "It's clear there are lots of radiation-hardened uses for this technology," Mortland said. Silicon oxide also works in reprogrammable gate arrays being built by NuPGA, a company formed last year through collaborative patents with Rice University. NuPGA's devices will assist in the design of computer circuitry based on vertical arrays of silicon oxide embedded in "vias," the holes in integrated circuits that connect layers of circuitry. Such rewritable gate arrays could drastically cut the cost of designing complex electronic devices.

Atrazine causes prostate inflammation in male rats and delays puberty

Wed, 25 Aug 2010 03:09:16 PDT

A new study shows that male rats prenatally exposed to low doses of atrazine, a widely used herbicide, are more likely to develop prostate inflammation and to go through puberty later than non-exposed animals. The research adds to a growing body of literature on atrazine, an herbicide predominantly used to control weeds and grasses in crops such as corn and sugar cane. Atrazine and its byproducts are known to be relatively persistent in the environment, potentially finding their way into water supplies. The research, which is available online and will be featured on the cover of Reproductive Toxicology (Volume 30, Issue 4), found that the incidence of prostate inflammation went from 48 percent in the control group to 81 percent in the male offspring who were exposed to a mixture of atrazine and its breakdown products prenatally. The severity of the inflammation increased with the strength of the doses. Puberty was also delayed in the animals who received atrazine. The doses of atrazine mixture given to the rats during the last five days of their pregnancy are close to the regulated levels in drinking water sources. The current maximum contamination level of atrazine allowed in drinking water is 3 parts per billion. The doses given to the animals were 0.09 (or 2.5 parts per million), 0.87, or 8.73 milligrams per kilogram body weight. The research was led by Suzanne Fenton, Ph.D., and Jason Stanko, Ph.D., of the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. Fenton began the work as a researcher at the United States Environmental Protection Agency (EPA), but completed the research at NIEHS, working closely with NIEHS pathologists. Both NIEHS and EPA provided financial support for the study. "We didn't expect to see these kinds of effects at such low levels," Fenton said. She adds that this is the second paper to show low dose effects of atrazine metabolite mixtures. Fenton was the senior author on a 2007 paper which demonstrated low doses of the atrazine mix delayed mammary development in female siblings from the same litters used in this current study. "It was noteworthy that the prostate inflammation decreased over time, suggesting the effects may not be permanent," said David Malarkey, D.V.M., Ph.D., an NIEHS pathologist and co-author on the paper. Fenton points out that these findings may extend beyond atrazine alone, and may be relevant to other herbicides found in the same chlorotriazine family, including propazine and simazine. All three of the herbicides create the same set of breakdown products. Fenton says more research is needed to understand the mechanism of action of the chlorotriazines and their metabolites on mammary and prostate tissue. "These tissues seem to be particularly sensitive to the effects of atrazine and its breakdown products," Fenton added. "The effects may be due to the stage of fetal development at the time the animals were exposed." "We hope that this information will be useful to the EPA, as it completes its risk assessment of atrazine," said Linda Birnbaum, Ph.D., director of NIEHS and the National Toxicology Program. Fenton will be presenting her research findings in September to the EPA, as part of its reassessment of atrazine. EPA announced in 2009 that it had begun a comprehensive new evaluation of atrazine to determine its effects on humans. At the end of this process, the agency will decide whether to revise its current risk assessment of atrazine and whether new restrictions are necessary to better protect public health. For more information about the EPA risk assessment, please visit http://www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm.

Scientist IDs genes that promise to make biofuel production more efficient, economical

Fri, 20 Aug 2010 03:22:33 PDT

A University of Illinois metabolic engineer has taken the first step toward the more efficient and economical production of biofuels by developing a strain of yeast with increased alcohol tolerance. Biofuels are produced through microbial fermentation of biomass crops, which yield the alcohol-based fuels ethanol and iso-butanol if yeast is used as the microbe to convert sugars from biomass into biofuels. "However, at a certain concentration, the biofuels that are being created become toxic to the yeast used in making them. Our goal was to find a gene or genes that reduce this toxic effect," said Yong-Su Jin, an assistant professor of microbial genomics in the U of I Department of Food Science and Human Nutrition and a faculty member in the U of I's Institute for Genomic Biology. Jin worked with Saccharomyces cerevisiae, the microbe most often used in making ethanol, to identify four genes (MSN2, DOG1, HAL1, and INO1) that improve tolerance to ethanol and iso-butanol when they are overexpressed. "We expect these genes will serve as key components of a genetic toolbox for breeding yeast with high ethanol tolerance for efficient ethanol fermentation," he said. To assess the overexpressed genes' contribution to the components that have limited biofuel production, the scientists tested them in the presence of high concentrations of glucose (10%), ethanol (5%), and iso-butanol (1%) and compared their performance to a control strain of S. cerevisiae. Overexpression of any of the four genes remarkably increased ethanol tolerance, but the strain in which INO1 was overexpressed elicited the highest ethanol yield and productivity—with increases of more than 70 percent for ethanol volume and more than 340 percent for ethanol tolerance when compared to the control strain. According to Jin, the functions of the identified genes are very diverse and unrelated, which suggests that tolerance to high concentrations of iso-butanol and ethanol might involve the complex interactions of many genetic elements in yeast. "For example, some genes increase cellular viability at the expense of fermentation. Others are more balanced between these two functions," he said. "Identification of these genes should enable us to produce transportation fuels from biomass more economically and efficiently. It's a first step in understanding the cellular reaction that currently limits the production process," he said. Further study of these genes should increase alcohol tolerance even further, and that will translate into cost savings and greater efficiency during biofuel production, he added.

Nanoscale DNA sequencing could spur revolution in personal health care

Tue, 17 Aug 2010 03:52:07 PDT

In experiments with potentially broad health care implications, a research team led by a University of Washington physicist has devised a method that works at a very small scale to sequence DNA quickly and relatively inexpensively. That could open the door for more effective individualized medicine, for example providing blueprints of genetic predispositions for specific conditions and diseases such as cancer, diabetes or addiction. "The hope is that in 10 years people will have all their DNA sequenced, and this will lead to personalized, predictive medicine," said Jens Gundlach, a UW physics professor and lead author of a paper describing the new technique published the week of Aug. 16 in the Proceedings of the National Academy of Sciences. The technique creates a DNA reader that combines biology and nanotechnology using a nanopore taken from Mycobacterium smegmatis porin A. The nanopore has an opening 1 billionth of a meter in size, just large enough to measure a single strand of DNA as it passes through. The scientists placed the pore in a membrane surrounded by potassium-chloride solution. A small voltage was applied to create an ion current flowing through the nanopore, and the current's electrical signature changed depending on the nucleotides traveling through the nanopore. Each of the nucleotides that are the essence of DNA – cytosine, guanine, adenine and thymine – produced a distinctive signature. The team had to solve two major problems. One was to create a short and narrow opening just large enough to allow a single strand of DNA to pass through the nanopore and for only a single DNA molecule to be in the opening at any time. Michael Niederweis at the University of Alabama at Birmingham modified the M. smegmatis bacterium to produce a suitable pore. The second problem, Gundlach said, was that the nucleotides flowed through the nanopore at a rate of one every millionth of a second, far too fast to sort out the signal from each DNA molecule. To compensate, the researchers attached a section of double-stranded DNA between each nucleotide they wanted to measure. The second strand would briefly catch on the edge of the nanopore, halting the flow of DNA long enough for the single nucleotide to be held within the nanopore DNA reader. After a few milliseconds, the double-stranded section would separate and the DNA flow continued until another double strand was encountered, allowing the next nucleotide to be read. The delay, though measured in thousandths of a second, is long enough to read the electrical signals from the target nucleotides, Gundlach said. "We can practically read the DNA sequence from an oscilloscope trace," he said. Besides Gundlach and Niederweiss, other authors are Ian Derrington, Tom Butler, Elizabeth Manrao and Marcus Collins of the UW; and Mikhail Pavlenok at Alabama-Birmingham. The work was funded by the National Institutes of Health and its National Human Genome Research Institute as part of a program to create technology to sequence a human genome for $1,000 or less. That program began in 2004, when it cost on the order of $10 million to sequence a human-sized genome. The new research is a major step toward achieving DNA sequencing at a cost of $1,000 or less. "Our experiments outline a novel and fundamentally very simple sequencing technology that we hope can now be expanded into a mechanized process," Gundlach said.

Probing the nanoparticle: Predicting how nanoparticles will react in the human body

Mon, 16 Aug 2010 03:11:55 PDT

Researchers at North Carolina State University have developed a method for predicting the ways nanoparticles will interact with biological systems – including the human body. Their work could have implications for improved human and environmental safety in the handling of nanomaterials, as well as applications for drug delivery. NC State researchers Dr. Jim Riviere, Burroughs Wellcome Distinguished Professor of Pharmacology and director of the university's Center for Chemical Toxicology Research and Pharmacokinetics, Dr. Nancy Monteiro-Riviere, professor of investigative dermatology and toxicology, and Dr. Xin-Rui Xia, research assistant professor of pharmacology, wanted to create a method for the biological characterization of nanoparticles – a screening tool that would allow other scientists to see how various nanoparticles might react when inside the body. "We wanted to find a good, biologically relevant way to determine how nanomaterials react with cells," Riviere says. "When a nanomaterial enters the human body, it immediately binds to various proteins and amino acids. The molecules a particle binds with will determine where it will go." This binding process also affects the particle's behavior inside the body. According to Monteiro-Riviere, the amino acids and proteins that coat a nanoparticle change its shape and surface properties, potentially enhancing or reducing characteristics like toxicity or, in medical applications, the particle's ability to deliver drugs to targeted cells. To create their screening tool, the team utilized a series of chemicals to probe the surfaces of various nanoparticles, using techniques previously developed by Xia. A nanoparticle's size and surface characteristics determine the kinds of materials with which it will bond. Once the size and surface characteristics are known, the researchers can then create "fingerprints" that identify the ways that a particular particle will interact with biological molecules. These fingerprints allow them to predict how that nanoparticle might behave once inside the body. The study results appear in the Aug. 23 online edition of Nature Nanotechnology. "This information will allow us to predict where a particular nanomaterial will end up in the human body, and whether or not it will be taken up by certain cells," Riviere adds. "That in turn will give us a better idea of which nanoparticles may be useful for drug delivery, and which ones may be hazardous to humans or the environment."

New nanoscale transistors allow sensitive probing inside cells

Fri, 13 Aug 2010 03:55:47 PDT

Chemists and engineers at Harvard University have fashioned nanowires into a new type of V-shaped transistor small enough to be used for sensitive probing of the interior of cells. The new device, described this week in the journal Science, is smaller than many viruses and about one-hundredth the width of the probes now used to take cellular measurements, which can be nearly as large as the cells themselves. Its slenderness is a marked improvement over these bulkier probes, which can damage cells upon insertion, reducing the accuracy or reliability of any data gained. "Our use of these nanoscale field-effect transistors, or nanoFETs, represents the first totally new approach to intracellular studies in decades, as well as the first measurement of the inside of a cell with a semiconductor device," says senior author Charles M. Lieber, the Mark Hyman, Jr. Professor of Chemistry at Harvard. "The nanoFETs are the first new electrical measurement tool for intracellular studies since the 1960s, during which time electronics have advanced considerably." Lieber and colleagues say nanoFETs could be used to measure ion flux or electrical signals in cells, particularly neurons. The devices could also be fitted with receptors or ligands to probe for the presence of individual biochemicals within a cell. Human cells can range in size from about 10 microns (millionths of a meter) for nerve cells to 50 microns for cardiac cells. While current probes measure up to 5 microns in diameter, nanoFETs are several orders of magnitude smaller: less than 50 nanometers (billionths of a meter) in total size, with the nanowire probe itself measuring just 15 nanometers in diameter. Aside from their small size, two features allow for easy insertion of nanoFETs into cells. First, Lieber and colleagues found that by coating the structures with a phospholipid bilayer – the same material cell membranes are made of – the devices are easily pulled into a cell via membrane fusion, a process related to that used to engulf viruses and bacteria. "This eliminates the need to push the nanoFETs into a cell, since they are essentially fused with the cell membrane by the cell's own machinery," Lieber says. "This also means insertion of nanoFETs is not nearly as traumatic to the cell as current electrical probes. We found that nanoFETs can be inserted and removed from a cell multiple times without any discernible damage to the cell. We can even use them to measure continu-ously as the device enters and exits the cell." Secondly, the current paper builds upon previous work by Lieber's group to introduce triangular "stereocenters" – essentially, fixed 120º joints – into nanowires, structures that had previously been rigidly linear. These stereocenters, analogous to the chemical hubs found in many complex organic molecules, introduce kinks into 1-D nanostructures, transforming them into more complex forms. Lieber and his co-authors found that introducing two 120º angles into a nanowire in the proper cis orientation creates a single V-shaped 60º angle, perfect for a two-pronged nanoFET with a sensor at the tip of the V. The two arms can then be connected to wires to create a current through the nanoscale transistor.

How many nanoparticles heat the tumor?

Tue, 10 Aug 2010 03:47:45 PDT

Those who have to fight a powerful enemy must look for allies. This is why physicists from different scientific fields have decided to cooperate with biomedical physicians in order to place the fight against cancer through heat treatment by means of magnetic nanoparticles on a solid, scientific basis. It is the objective of the cooperation to improve the success of the therapy. Within the scope of a joint project funded by the Deutsche Forschungsgemeinschaft, Melanie Kettering from the Institut für Diagnostische und Interventionelle Radiologie (IDIR), University Hospital Jena, and Heike Richter from the Physikalisch-Technische Bundesanstalt (PTB) are responsible for the task of detecting where many magnetic nanoparticles can be found in the body of the patient. They are injected into the tumour - but do they really remain there or are they distributed throughout the body? Knowing how many are in the tumour is important for the success of the heat treatment. Now the scientists have been able to successfully demonstrate on mice that magnetic relaxometry is suited to be applied together with the heat treatment. It furnishes information about the whereabouts of the nanoparticles in the body – completely without contact to the patient. For cancer therapy by means of heat treatment, magnetic nanoparticles are injected into the tumour and excited by an external electromagnetic a.c. field. Through this, the magnetic nanoparticles generate heat inside the tumour. If temperatures between 55 °C and 60 °C are reached, cancer cells can be destroyed irreversibly. The surrounding healthy tissue (without magnetic nanoparticles) remains unaffected. The procedure has not yet found its way into clinical routine, but is still in the trial phase, as a series of questions still have to be clarified. Among other things, a procedure is required which shows where the nanoparticles are located in the body and in which quantity they can be found there. On this basis, a selective treatment of the tumour can be achieved. PTB scientists have found out that magnetic relaxometry is very well suited to obtain this information – without even touching the body of the patient or harming her/him in another way. This is done as follows before the treatment as such is started: The ferric oxide nanoparticles injected into the tumour are superparamagnetic, i.e. they are small magnetic particles which can change their magnetization direction independently of one another. At room temperature, their orientation in the room is statistically distributed so that their sum does not form a magnetic moment. If an external constant magnetic field is now applied, they all orientate themselves almost identically in the room along the field and generate a magnetic moment which can be measured from the outside. This magnetic field is then switched off and with sensitive magnetic field sensors, so-called SQUIDs (Superconducting QUantum Interference Devices, superconducting quantum interference units), the following relaxation of the magnetization - i.e. the return of the magnetic moment from the uniform orientation towards a state with a statistic distribution - is determined extremely promptly. The amplitude of the relaxation signal then provides information about the particle quantity. The investigations carried out so far on mice allow the conclusion to be drawn that the injection of magnetic nanoparticles and the whereabouts of the particles at the place of injection work variably well. In some tumours, the scientists could find - 24 hours after the injection - the almost complete amount of nanoparticles in the cancer, whereas in other tumours only one quarter of the injected particles could be detected. Up to now, it has not been possible to find a well-founded explanation for these different quantities of magnetic nanoparticles in the tumour. However, the result shows all the more how important it is to apply magnetic relaxometry concurrently with the heat treatment of cancer by nanoparticles to be able to make statements about the quantity of particles in the tumour. (ptb/if)

NIST nanofluidic 'multi-tool' separates and sizes nanoparticles

Thu, 05 Aug 2010 03:41:25 PDT

A wrench or a screwdriver of a single size is useful for some jobs, but for a more complicated project, you need a set of tools of different sizes. Following this guiding principle, researchers at the National Institute of Standards and Technology (NIST) have engineered a nanoscale fluidic device that functions as a miniature "multi-tool" for working with nanoparticles—objects whose dimensions are measured in nanometers, or billionths of a meter. First introduced in March 2009 (see "NIST-Cornell Team Builds World's First Nanofluidic Device with Complex 3-D Surfaces", the device consists of a chamber with a cascading "staircase" of 30 nanofluidic channels ranging in depth from about 80 nanometers at the top to about 620 nanometers (slightly smaller than an average bacterium) at the bottom. Each of the many "steps" of the staircase provides another "tool" of a different size to manipulate nanoparticles in a method that is similar to how a coin sorter separates nickels, dimes and quarters. In a new article in the journal Lab on a Chip*, the NIST research team demonstrates that the device can successfully perform the first of a planned suite of nanoscale tasks—separating and measuring a mixture of spherical nanoparticles of different sizes (ranging from about 80 to 250 nanometers in diameter) dispersed in a solution. The researchers used electrophoresis—the method of moving charged particles through a solution by forcing them forward with an applied electric field—to drive the nanoparticles from the deep end of the chamber across the device into the progressively shallower channels. The nanoparticles were labeled with fluorescent dye so that their movements could be tracked with a microscope. As expected, the larger particles stopped when they reached the steps of the staircase with depths that matched their diameters of around 220 nanometers. The smaller particles moved on until they, too, were restricted from moving into shallower channels at depths of around 110 nanometers. Because the particles were visible as fluorescent points of light, the position in the chamber where each individual particle was stopped could be mapped to the corresponding channel depth. This allowed the researchers to measure the distribution of nanoparticle sizes and validate the usefulness of the device as both a separation tool and reference material. Integrated into a microchip, the device could enable the sorting of complex nanoparticle mixtures, without observation, for subsequent application. This approach could prove to be faster and more economical than conventional methods of nanoparticle sample preparation and characterization. The NIST team plans to engineer nanofluidic devices optimized for different nanoparticle sorting applications. These devices could be fabricated with tailored resolution (by increasing or decreasing the step size of the channels), over a particular range of particle sizes (by increasing or decreasing the maximum and minimum channel depths), and for select materials (by conforming the surface chemistry of the channels to optimize interaction with a specific substance). The researchers are also interested in determining if their technique could be used to separate mixtures of nanoparticles with similar sizes but different shapes—for example, mixtures of tubes and spheres.

Cells use water in nano-rotors to power energy conversion

Wed, 04 Aug 2010 04:23:00 PDT

Researchers from the Max Planck Institute of Biophysics in Frankfurt, and Mount Sinai School of Medicine in New York have provided the first atomic-level glimpse of the proton-driven motor from a major group of ATP synthases, enzymes that are central to cellular energy conversion. The study, by Dr. Thomas Meier, his PhD student Laura Preiss and Dr. Özkan Yildiz of the Max-Planck Institute, and Drs. Terry Krulwich and David Hicks of Mount Sinai, revealed a water molecule in the critical rotor element of a bacterial nano-motor that shares common features with the rotors of ATP synthases from human mitochondria and from diverse bacteria, including pathogens such as Mycobacterium tuberculosis, in which the ATP synthase is a drug target. The paper publishes next week in the online, open access journal PLoS Biology. ATP synthases are among the most abundant and important proteins in living cells. These rotating nano-machines produce the central chemical form of cellular energy currency, ATP (adenosine triphosphate), which is used to meet the energy needs of cells. For example, human adults synthesize up to 75 kg of ATP each day under resting conditions and need a lot more to keep pace with energy needs during strenuous exercise or work. The turbine of the ATP synthase is the rotor element, called the c-ring. This ring is 63 Å in diameter (6.3 nm, or 6.3 millionths of a millimeter) and completes over 500 rotations per second during ATP production. The researchers from Frankfurt and New York were able to grow three-dimensional protein crystals of the unusually stable rotor ring from a Bacillus that can grow under extremely low-proton (alkaline) conditions. The molecular architecture of this turbine was determined using X-ray crystallography. The researchers were surprised by the results and excited by the promise they hold for future mechanistic insights into the structure and function of ATP synthases. Dr. Meier states: "We did not expect a water molecule to be a key player in this group of rotors. This atomic structure gives us a new and much better framework for understanding how these proton-driven nano-machines work, how they capture the protons that fuel rotation and how they hold on to them through rotation. The results join other recent examples of the usefulness of unusual organisms, such as this 'extremophilic' bacillus, in providing insights into fundamental life processes and we look forward to further collaborative work on different forms of this rotor. Further basic research into the structural and mechanistic details of ATP synthase nano-machines will impact both nanotechnology and medicine and, perhaps, areas in which nanotechnology converges with medicine."

Iron oxide nanoparticles becoming tools for brain tumor imaging and treatment

Tue, 03 Aug 2010 03:07:10 PDT

Tiny particles of iron oxide could become tools for simultaneous tumor imaging and treatment, because of their magnetic properties and toxic effects against brain cancer cells. In mice, researchers from Emory University School of Medicine have demonstrated how these particles can deliver antibodies to implanted brain tumors, while enhancing tumor visibility via magnetic resonance imaging (MRI). The results are published online by the journal Cancer Research. The lead author is Costas Hadjipanayis, assistant professor of neurosurgery at Emory University School of Medicine, director of Emory's Brain Tumor Nanotechnology Laboratory, and chief of neurosurgery service at Emory University Hospital Midtown. Glioblastoma multiforme (GBM), the most common and most aggressive primary brain tumor, often comes back because cancer cells infiltrate into the surrounding brain tissue and survive initial treatment. Hadjipanayis' team designed tiny iron oxide particles (10 nanometers across), coated with a polymer and bioconjugated or linked to antibodies directed against a molecule that appears on the surface of glioblastoma cells. This molecule, a shortened and continuously active form of the epidermal growth factor receptor (EGFRvIII), drives glioblastoma cell growth and accounts for radiation and chemotherapy resistance. EGFRvIII appears in about a third of glioblastomas and is only present on tumor cells and not the normal surrounding cells in the brain. The team showed that the particles bind to and kill human glioblastoma cells, yet do not cause any toxicity to normal human astrocytes, which comprise the majority of cells in the brain. They used a technique called convection-enhanced delivery (CED) – continuous infusion of fluid under positive pressure – to introduce the iron oxide particles into mice that had human glioblastoma cells implanted intracranially. The antibody-linked particles lengthened survival of the tumor-implanted mice: their median survival was 19 days compared to 16 days for bare particles and 11 days for no particles. The particles also made the tumor visible via MRI, darkening the area of the brain where the tumor is (see accompanying image). Hui Mao, PhD associate professor of radiology, and his team of researchers, contributed MRI experiments showing the sensitive imaging qualities of the iron-oxide nanoparticles in vitro and in the mouse brain. To heighten anti-cancer effects, the Brain Tumor Nanotechnology Laboratory is investigating the use of safe alternating magnetic fields for the generation of local hyperthermia (heating) against malignant brain tumors by magnetic nanoparticles. Hadjipanayis and his team plan to translate the use of bioconjugated iron-oxide nanoparticles for use in canine brain tumor models at the University of Georgia College of Veterinary Medicine and into a human clinical trial for patients suffering from brain cancer.

Novel bee venom derivative forms a nanoparticle 'smart bomb' to target cancer cells

Tue, 03 Aug 2010 02:59:43 PDT

The next time you are stung by a bee, here's some consolation: a toxic protein in bee venom, when altered, significantly improves the effectiveness liposome-encapsulated drugs or dyes, such as those already used to treat or diagnose cancer. This research, described in the August 2010 print issue of the FASEB Journal (http://www.fasebj.org), shows how modified melittin may revolutionize treatments for cancer and perhaps other conditions, such as arthritis, cardiovascular disease, and serious infections. "This type of transporter agent may help in the design and use of more personalized treatment regimens that can be selectively targeted to tumors and other diseases," said Samuel A. Wickline, Ph.D., a researcher involved in the work from the Consortium for Translational Research in Advanced Imaging and Nanomedicine (C-TRAIN) at the Washington University School of Medicine in St. Louis, Missouri. To make this discovery, Wickline and colleagues designed and tested variations of the melittin protein to derive a stable compound that could be inserted into liposomal nanoparticles and into living cells without changing or harming them. They then tested the ability of this protein, or "transporter agent," to attach to different therapeutic compounds and enhance drug therapy without causing harmful side effects. In addition, their results suggest that the base compound which is used to create the transporter agent may improve tumor therapy as well. "Our journal is abuzz in a hive of bee-related discoveries. Just last month, we published research showing for the first time how honey kills bacteria. This month, the Wickline study shows how bee venom peptides can form "smart bombs" that deliver liposomal nanoparticles directly to their target, without collateral damage," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal.

Kinked nanopores slow DNA passage for easier sequencing

Sat, 31 Jul 2010 04:55:56 PDT

In an innovation critical to improved DNA sequencing, a markedly slower transmission of DNA through nanopores has been achieved by a team led by Sandia National Laboratories researchers. Solid-state nanopores sculpted from silicon dioxide are generally straight, tiny tunnels more than a thousand times smaller than the diameter of a human hair. They are used as sensors to detect and characterize DNA, RNA and proteins. But these materials shoot through such holes so rapidly that sequencing the DNA passing through them, for example, is a problem. In a paper published this week online (July 23) in Nature Materials (hardcopy slated for August, Vol.9, pp. 667-675), a team led by Sandia National Laboratories researchers reports using self-assembly techniques to fabricate equally tiny but kinked nanopores. Combined with atomic-layer deposition to modify the chemical characteristics of the nanopores, the innovations achieve a fivefold slowdown in the voltage-driven translocation speeds critically needed in DNA sequencing. (Translocation involves DNA entering and passing completely through the pores, which are only slightly wider than the DNA itself.) “By control of pore size, length, shape and composition,” says lead researcher Jeff Brinker, “we capture the main functional behaviors of protein pores in our solid-state nanopore system.” The importance of a fivefold slowdown in this kind of work, Brinker says, is large. Also of note is the technique’s capability to separate single- and double-stranded DNA in an array format. “There are promising DNA sequencing technologies that require this,” says Brinker. The idea of using synthetic solid-state nanopores as single-molecule sensors for detection and characterization of DNA and its sister materials is currently under intensive investigation by researchers around the world. The thrust was inspired by the exquisite selectivity and flux demonstrated by natural biological channels. Researchers hope to emulate these behaviors by creating more robust synthetic materials more readily integrated into practical devices. Current scientific procedures align the formation of nominally cylindrical or conical pores at right angles to a membrane surface. These are less capable of significantly slowing the passage of DNA than the kinked nanopores. “We had a pretty simple idea,” Brinker says. “We use the self-assembly approaches we pioneered to make ultrathin membranes with ordered arrays of about 3-nanometer diameter pores. We then further tune the pore size via an atomic-layer deposition process we invented. This allows us to control the pore diameter and surface chemistry at the subnanometer scale. Compared to other solid state nanopores developed to date, our system combines finer control of pore size with the development of a kinked pore pathway. In combination, these allow slowing down the DNA velocity.” The work is supported by the Air Force Office of Scientific Research, the Department of Energy’s Basic Energy Sciences and Sandia’s Laboratory Directed Research and Development office. In addition to Brinker, participating team members include Sandians David Adams, Carter Hodges and former Sandia post-doctoral student Yingbing Jiang, with University of New Mexico (UNM) researchers Zhu Chen, Darren Dunphy, Nanguo Liu, and George Xomeritakas. Other research participants are from the UNM School of Pharmacy, the University of Illinois at Urbana-Champaign’s Beckman Institute and Mechanical Science and Engineering Dept., and Purdue University’s School of Chemical Engineering. Brinker is a Sandia Fellow, and Distinguished and Regent’s Professor of Chemical and Nuclear Engineering and Molecular Genetics and Microbiology at UNM.

Nanotechnology for water purification

Thu, 29 Jul 2010 06:23:21 PDT

Nanotechnology refers to a broad range of tools, techniques and applications that simply involve particles on the approximate size scale of a few to hundreds of nanometers in diameter. Particles of this size have some unique physicochemical and surface properties that lend themselves to novel uses. Indeed, advocates of nanotechnology suggest that this area of research could contribute to solutions for some of the major problems we face on the global scale such as ensuring a supply of safe drinking water for a growing population, as well as addressing issues in medicine, energy, and agriculture. Writing in the International Journal of Nuclear Desalination, researchers at the D.J. Sanghvi College of Engineering, in Mumbai, India, explain that there are several nanotechnology approaches to water purification currently being investigated and some already in use. "Water treatment devices that incorporate nanoscale materials are already available, and human development needs for clean water are pressing," Alpana Mahapatra and colleagues Farida Valli and Karishma Tijoriwala, explain. Water purification using nanotechnology exploits nanoscopic materials such as carbon nanotubes and alumina fibers for nanofiltration, it also utilizes the existence of nanoscopic pores in zeolite filtration membranes, as well as nanocatalysts and magnetic nanoparticles. Nanosensors, such as those based on titanium oxide nanowires or palladium nanoparticles are used for analytical detection of contaminants in water samples. The impurities that nanotechnology can tackle depend on the stage of purification of water to which the technique is applied, the team adds. It can be used for removal of sediments, chemical effluents, charged particles, bacteria and other pathogens. They explain that toxic trace elements such as arsenic, and viscous liquid impurities such as oil can also be removed using nanotechnology. "The main advantages of using nanofilters, as opposed to conventional systems, are that less pressure is required to pass water across the filter, they are more efficient, and they have incredibly large surface areas and can be more easily cleaned by back-flushing compared with conventional methods," the team says. For instance, carbon nanotube membranes can remove almost all kinds of water contaminants including turbidity, oil, bacteria, viruses and organic contaminants. Although their pores are significantly smaller carbon nanotubes have shown to have an equal or a faster flow rate as compared to larger pores, possibly because of the smooth interior of the nanotubes. Nanofibrous alumina filters and other nanofiber materials also remove negatively charged contaminants such as viruses, bacteria, and organic and inorganic colloids at a faster rate than conventional filters. "While the current generation of nanofilters may be relatively simple, it is believed that future generations of nanotechnology-based water treatment devices will capitalize on the properties of new nanoscale materials," the team says. The researchers point out that several fundamental aspects of nanotechnology have raised concerns among the public and activist groups. They concede that the risks associated with nanomaterials may not be the same as the risks associated with the bulk versions of the same materials because the much greater surface area to volume ratio of nanoparticles can make them more reactive than bulk materials and lead to so far unrecognized and untested interactions with biological surfaces. Water purification based on nanotechnology has not yet led to any human health or environmental problems but the team echoes the sentiment of others that further research into the biological interactions of nanoparticles should be carried out.

Multifunctional nanoparticle enables new type of biological imaging

Wed, 28 Jul 2010 04:29:01 PDT

Spotting a single cancerous cell that has broken free from a tumor and is traveling through the bloodstream to colonize a new organ might seem like finding a needle in a haystack. But a new imaging technique from the University of Washington is a first step toward making this possible. UW researchers have developed a multifunctional nanoparticle that eliminates the background noise, enabling a more precise form of medical imaging – essentially erasing the haystack, so the needle shines through. A successful demonstration with photoacoustic imaging was reported today (July 27) in the journal Nature Communications. Nanoparticles are promising contrast agents for ultrasensitive medical imaging. But in all techniques that do not use radioactive tracers, the surrounding tissues tend to overwhelm weak signals, preventing researchers from detecting just one or a few cells. "Although the tissues are not nearly as effective at generating a signal as the contrast agent, the quantity of the tissue is much greater than the quantity of the contrast agent and so the background signal is very high," said lead author Xiaohu Gao, a UW assistant professor of bioengineering. The newly presented nanoparticle solves this problem by for the first time combining two properties to create an image that is different from what any existing technique could have produced. The new particle combines magnetic properties and photoacoustic imaging to erase the background noise. Researchers used a pulsing magnetic field to shake the nanoparticles by their magnetic cores. Then they took a photoacoustic image and used image processing techniques to remove everything except the vibrating pixels. Gao compares the new technique to "Tourist Remover" photo editing software that allows a photographer to delete other people by combining several photos of the same scene and keeping only the parts of the image that aren't moving. "We are using a very similar strategy," Gao said. "Instead of keeping the stationary parts, we only keep the moving part. "We use an external magnetic field to shake the particles," he explained. "Then there's only one type of particle that will shake at the frequency of our magnetic field, which is our own particle." Experiments with synthetic tissue showed the technique can almost completely suppress a strong background signal. Future work will try to duplicate the results in lab animals, Gao said. The 30-nanometer particle consists of an iron-oxide magnetic core with a thin gold shell that surrounds but does not touch the center. The gold shell is used to absorb infrared light, and could also be used for optical imaging, delivering heat therapy, or attaching a biomolecule that would grab on to specific cells. Earlier work by Gao's group combined functions in a single nanoparticle, something that is difficult because of the small size. "In nanoparticles, one plus one is often less than two," Gao said. "Our previous work showed that one plus one can be equal to two. This paper shows that one plus one is, finally, greater than two." The first biological imaging, in the 1950s, was used to identify anatomy inside the body, detecting tumors or fetuses. The second generation has been used to monitor function – fMRI, or functional magnetic resonance imaging, for example, detects oxygen use in the brain to produce a picture of brain activity. The next generation of imaging will be molecular imaging, said co-author Matthew O'Donnell, a UW professor of bioengineering and engineering dean. This will mean that medical assays and cell counts can be done inside the body. In other words, instead of taking a biopsy and inspecting tissue under a microscope, imaging could detect specific proteins or abnormal activity at the source. But making this happen means improving the confidence limits of the imaging. "Today, we can use biomarkers to see where there's a large collection of diseased cells," O'Donnell said. "This new technique could get you down to a very precise level, potentially of a single cell." Researchers tested the method for photoacoustic imaging, a low-cost method now being developed that is sensitive to slight variations in tissues' properties and can penetrate several centimeters in soft tissue. It works by using a pulse of laser light to heat a cell very slightly. This heat causes the cell to vibrate and produce ultrasound waves that travel through the tissue to the body's surface. The new technique should also apply to other types of imaging, the authors said.

Nanoblasts from laser-activated nanoparticles move molecules, proteins and DNA into cells

Wed, 28 Jul 2010 04:14:50 PDT

Using chemical "nanoblasts" that punch tiny holes in the protective membranes of cells, researchers have demonstrated a new technique for getting therapeutic small molecules, proteins and DNA directly into living cells. Carbon nanoparticles activated by bursts of laser light trigger the tiny blasts, which open holes in cell membranes just long enough to admit therapeutic agents contained in the surrounding fluid. By adjusting laser exposure, the researchers administered a small-molecule marker compound to 90 percent of targeted cells – while keeping more than 90 percent of the cells alive. The research was sponsored by the National Institutes of Health and the Institute of Paper Science and Technology at Georgia Tech. It will be reported in the August issue of the journal Nature Nanotechnology. "This technique could allow us to deliver a wide variety of therapeutics that now cannot easily get into cells," said Mark Prausnitz, a professor in the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology. "One of the most significant uses for this technology could be for gene-based therapies, which offer great promise in medicine, but whose progress has been limited by the difficulty of getting DNA and RNA into cells." The work is believed to be the first to use activation of reactive carbon nanoparticles by lasers for medical applications. Additional research and clinical trials will be needed before the technique could be used in humans. Researchers have been trying for decades to drive DNA and RNA more efficiently into cells with a variety of methods, including using viruses to ferry genetic materials into cells, coating DNA and RNA with chemical agents or employing electric fields and ultrasound to open cell membranes. However, these previous methods have generally suffered from low efficiency or safety concerns. With their new technique, which was inspired by earlier work on the so-called "photoacoustic effect," Prausnitz and collaborators Prerona Chakravarty, Wei Qian and Mostafa El-Sayed hope to better localize the application of energy to cell membranes, creating a safer and more efficient approach for intracellular drug delivery. Their technique begins with introducing particles of carbon black measuring 25 nanometers – one millionth of an inch – in diameter into the fluid surrounding the cells into which the therapeutic agents are to be introduced. Bursts of near-infrared light from a femotosecond laser are then applied to the fluid at a rate of 90 million pulses per second. The carbon nanoparticles absorb the light, which makes them hot. The hot particles then heat the surrounding fluid to make steam. The steam reacts with the carbon nanoparticles to form hydrogen and carbon monoxide. The two gases form a bubble which grows as the laser provides energy. The bubble collapses suddenly when the laser is turned off, creating a shock wave that punches holes in the membranes of nearby cells. The openings allow therapeutic agents from the surrounding fluid to enter the cells. The holes quickly close so the cell can survive. The researchers have demonstrated that they could get the small molecule calcein, the bovine serum albumin protein and plasmid DNA through the cell membranes of human prostate cancer cells and rat gliosarcoma cells using this technique. Calcein uptake was seen in 90 percent of the cells at laser levels that left more than 90 percent of the cells alive. "We could get almost all of the cells to take up these molecules that normally wouldn't enter the cells, and almost all of the cells remained alive," said Prerona Chakravarty, the study's lead author. "Our laser-activated carbon nanoparticle system enables controlled bubble implosions that can disrupt the cell membranes just enough to get the molecules in without causing lasting damage." To assess how long the holes in the cell membrane remained open, the researchers left the simulated therapeutics out of the fluid when the cells were exposed to the laser light, then added the agents one second after turning off the laser. They saw almost no uptake of the molecules, suggesting that the cell membranes resealed themselves quickly. To confirm that the carbon-steam reaction was a critical factor driving the nanoblasts, the researchers substituted gold nanoparticles for the carbon nanoparticles before exposure to laser light. Because they lacked the carbon needed for reaction, the gold nanoparticles produced little uptake of the molecules, Prausnitz noted. Similarly, the researchers substituted carbon nanotubes for the carbon nanoparticles, and also measured little uptake, which they explained by noting that the nanotubes are less reactive than the carbon black particles. Experimentation further showed that DNA introduced into cells through the laser-activated technique remained functional and capable of driving protein expression. When plasmid DNA that encoded for luciferase expression was introduced into the cancer cells, production of luciferase increased 17-fold. For the future, the researchers plan to study use of a less expensive nanosecond laser to replace the ultrafast femtosecond instrument used in the research. They also plan to optimize the carbon nanoparticles so that nearly all of them are consumed during the exposure to laser light. Leftover carbon nanoparticles in the body should produce no harmful effects, though the body may be unable to eliminate them, Prausnitz noted. "This is the first study showing proof of principle for laser-activation of reactive carbon nanoparticles for drug and gene delivery," he said. "There is a considerable path ahead before this can be brought into medicine, but we are optimistic that this approach can ultimately provide a new alternative for delivering therapeutic agents into cells safely and efficiently."

Noninvasive MR imaging of blood vessel growth in tumors using nanosized contrast agents

Fri, 23 Jul 2010 10:33:15 PDT

Formation of new blood vessels, also known as angiogenesis, is crucial for sustained tumor growth and cancer metastasis. Recently, clinically available therapies to suppress the growth of these vessels have been available to improve patient survival in some cancer types. Accurate detection and quantification of blood vessel growth using nonsurgical methods would greatly complement current therapies and allow physicians to quickly assess treatment regimens and adjust them as necessary. In the work published in the August issue of Experimental Biology and Medicine, Kessinger and coworkers have incorporated nanotechnology, material science, and the clinical imaging modality MRI, to create a nanosized probe capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model. The work was carried out by Chase Kessinger, as part of his PhD thesis in cancer molecular imaging, working together with Jinming Gao and other colleagues, at the University of Texas Southwestern Medical Center at Dallas. Dr. Gao stated "Imaging tumor angiogenesis is important in early detection, tumor stratification and post-therapy assessment of antiangiogenic drugs. Current clinical modality for angiogenesis imaging utilizes dynamic contrast enhancement MRI by small molecular contrast agents. The method is based on the measurement of permeability of the contrast probes in well-established solid tumors and is not very specific to detect the early on-set of vessel formation. The dual functional nanoprobes aim to image angiogenesis-specific tumor markers that are overly expressed in the tumor vasculature during the early phase of angiogenesis." Together, the research team relied on nanotechnology and established super paramagnetic micellar nanoprobes (50-70 nm in diameter) with greatly improved MRI sensitivity over conventional small molecular agents. The nanoprobe surface was functionalized with integrins that are a cyclic peptide that can specifically bind to overexpressed on the tumor endothelial cells. The nanoprobes also had a fluorescent moiety used for the validation of targeted delivery to the tumor endothelial cells. Studies in cancer cells validated the increased uptake of nanoprobes compared to non-targeted-nanoparticles. In collaboration with Dr. Masaya Takahashi and coworkers in the Advanced Imaging Research Center at UT Southwestern Medical Center, the research team employed a 3D high resolution acquisition method to visualize the accumulation of the micelle nanoprobes in tumors. Dr. Gao said "Conventional image analysis of angiogenesis relies on the evaluation of 'hot spot' densities in 2D images. The 3D high resolution method allowed for the connection of the isolated 'hot spots' in 2D slices into 3D network structures, which greatly improves the accuracy of vessel identification and quantification." In preclinical animal tumor models, MR imaging of the targeted contrast probes yielded vascularized network structures in 3D tumor images. The enhanced visualization allowed for a more accurate quantification of tumor angiogenesis. The results showed significant increase of contrast specificity of angiogenic vessels by the targeted nanoprobes over non-targeted micelles. These targeted nanoprobes may provide a useful contrast probe design for the clinical diagnosis of tumor angiogenesis. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "Kessinger et al working at the interface of nanotechnology, material science, and the clinical imaging modality MRI have created a nanosized probe capable of noninvasively visualizing and quantifying the blood vessel growth in tumors in a preclinical model. This should be an important tool for clinical observation of tumor angiogenesis".

Researchers use nanoparticles as destructive beacons to zap tumors

Thu, 22 Jul 2010 08:35:51 PDT

A group of researchers from Wake Forest University Baptist Medical Center is developing a way to treat cancer by using lasers to light up tiny nanoparticles and destroy tumors with the ensuing heat. Today at the 52nd Annual Meeting of the American Association of Physicists in Medicine (AAPM) in Philadelphia, they will describe the latest development for this technology: iron-containing Multi-Walled Carbon Nanotubes (MWCNTs) -- threads of hollow carbon that are 10 thousand times thinner than a human hair. In laboratory experiments, the team showed that by using an MRI scanner, they could image these particles in living tissue, watch as they approached a tumor, zap them with a laser, and destroy the tumor in the process. If this sounds like science fiction, it is not. The work builds on an experimental technique for treating cancer called laser-induced thermal therapy (LITT), which uses energy from lasers to heat and destroy tumors. LITT works by virtue of the fact that certain nanoparticles like MWCNTs can absorb the energy of a laser and then convert it into heat. If the nanoparticles are zapped while within a tumor, they will boil off the energy as heat and kill the cancerous cells. The problem with LITT, however, is that while a tumor may be clearly visible in a medical scan, the particles are not. They cannot be tracked once injected, which could put a patient in danger if the nanoparticles were zapped away from the tumor because the aberrant heating could destroy healthy tissue. Now the team from Wake Forest Baptist has shown for the first time that it is possible to make the particles visible in the MRI scanner to allow imaging and heating at the same time. By loading the MWCNT particles with iron, they become visible in an MRI scanner. Using tissue containing mouse tumors, they showed that these iron-containing MWCNT particles could destroy the tumors when hit with a laser. "To find the exact location of the nanoparticle in the human body is very important to the treatment," says Xuanfeng Ding, M.S., who is presenting the work today in Philadelphia. "It is really exciting to watch the tumor labeled with the nanotubes begin to shrink after the treatment." The results are part of Ding's ongoing Ph.D. thesis work -- a multi-disciplinary project led by Suzy Torti, Ph.D., professor of biochemistry at Wake Forest Baptist, and David Carroll, Ph.D., director of the Wake Forest University Center for Nanotechnology and Molecular Materials, that also includes the WFB Departments of Physics, Radiation Oncology, Cancer Biology, and Biochemistry. A previous study by the same group showed that laser-induced thermal therapy using a closely-related nanoparticle actually increased the long-term survival of mice with tumors. The next step in this project is to see if the iron-loaded nanoparticles can do the same thing. If the work proves successful, it may one day help people with cancer, though the technology would have to prove safe and effective in clinical trials. Dan Bourland, Ph.D., associate professor of radiation oncology and Ding's advisor, praises the high quality of Ding's work and says that the project is a strong example of today's "team science" that is needed for success in the biomedical fields.

K-State researchers find gene-silencing nanoparticles may put end to pesky summer pest

Tue, 20 Jul 2010 05:04:04 PDT

Summer just wouldn't be complete without mosquitoes nipping at exposed skin. Or would it? Research conducted by a Kansas State University team may help solve a problem that scientists and pest controllers have been itching to for years. Kun Yan Zhu, professor of entomology, and teammates Xin Zhang, graduate student in entomology from China, and Jianzhen Zhang, a visiting scientist from Shanxi University, China, investigated using nanoparticles to deliver double-stranded ribonucleic acid, dsRNA -- a molecule capable of specifically triggering gene silencing -- into mosquito larvae through their food. By silencing particular genes, Zhu said the dsRNA may kill the developing mosquitoes or make them more susceptible to pesticides. Gene silencing triggered by dsRNA or small interfering RNA, siRNA, is known as RNA interference, or RNAi. "RNAi is a specific and effective approach for loss of function studies in virtually all eukaryotic organisms," Zhu said. Eukaryotic organisms have cells that contain a nucleus within which genetic material is carried and can therefore be manipulated. Almost all animals, plants and fungi are eukaryotes. Once RNAi is triggered, it destroys the messenger RNA, or mRNA, of a particular gene. This prevents the translation of the gene into its product, silencing it. In the case of Zhu's research, RNAi was used to silence genes responsible for the production of chitin, the principle constituent of the exoskeleton in insects, crustaceans and arachnids. "Since our RNAi is focused on chitin synthesis, the dsRNA that is delivered into the mosquito larvae can basically block the production of chitin," Zhu said. Though the silencing is not yet 100 percent effective in their study, Zhu said it does leave the mosquito's body with less ability to combat insecticides, which must penetrate the mosquito's exoskeleton. If the gene, called chitin synthase, could be completely silenced, the mosquitoes may die without the use of pesticides because the chitin biosynthesis pathway would be blocked, Zhu said. Zhu theorized using nanoparticles to deliver dsRNA to mosquito larvae might work because of the low success of manually injecting larvae with dsRNA. Mosquito larvae live in water but because dsRNA quickly dissipates in water, it can't be directly added to the larvae's food source. Zhu's group discovered that using nanoparticles assembled from dsRNA facilitates their ingestion by mosquito larvae because the nanoparticles don't dissolve in water. Zhu said the nanoparticles may also stabilize the dsRNA in water. "Now insects will have a much greater likelihood of getting these nanoparticles containing the dsRNA into their gut through feeding," Zhu said. Potentially, bait containing dsRNA-based nanoparticles could be developed for insect control, Zhu said. "Because we can select specific genes for silencing, and the nanoparticles are formed from chitosan -- a virtually non-toxic and biodegradable polymer -- this pest control technology could target specific pest species while being environmentally friendly," he said. Mosquitoes were chosen, Zhu said, because of the abundant research on them as human disease vectors. Other insects, though, can have their genes silenced. Zhu and his collaborators also have investigated gene silencing in the European corn borer and in grasshoppers, a major insect pest in China. Nanoparticles did not have to be used because grasshoppers and European corn borers are not aquatic. However, nanoparticle-based RNAi may facilitate the studies on the functions of new genes. The team's paper, "Chitosan/double-stranded RNA nanoparticle-mediated RNA interference to silence chitin synthase genes through larval feeding in African malaria mosquito (Anopheles gambiae)," was recently accepted by the journal, Insect Molecular Biology. It has been published online in advance of print. The research was partially funded by the Kansas Agricultural Experiment Station. Zhu's upcoming research will focus on gene silencing in agricultural pests.

New arsenic nanoparticle blocks aggressive breast cancer

Fri, 16 Jul 2010 03:35:54 PDT

You can teach an old drug new chemotherapy tricks. Northwestern University researchers took a drug therapy proven for blood cancers but ineffective against solid tumors, packaged it with nanotechnology and got it to combat an aggressive type of breast cancer prevalent in young women, particularly young African-American women. That drug is arsenic trioxide, long part of the arsenal of ancient Chinese medicine and recently adopted by Western oncologists for a type of leukemia. The cancer is triple negative breast cancer, which often doesn't respond well to traditional chemotherapy and can't be treated by potentially life-saving targeted therapies. Women with triple negative breast cancer have a high risk of the cancer metastasizing and poor survival rates. Prior to the new research, arsenic hadn't been effective in solid tumors. After the drug was injected into the bloodstream, it was excreted too rapidly to work. The concentration of arsenic couldn't be increased, because it was then too toxic. A new arsenic nanoparticle -- designed to slip undetected through the bloodstream until it arrives at the tumor and delivers its poisonous cargo -- solved all that. The nanoparticle, called a nanobin, was injected into mice with triple negative breast tumors. Nanobins loaded with arsenic reduced tumor growth in mice, while the non-encapsulated arsenic had no effect on tumor growth. The arsenic nanobins blocked tumor growth by causing the cancer cells to die by a process known as apoptosis. The nanobin consists of nanoparticulate arsenic trioxide encapsulated in a tiny fat vessel (a liposome) and coated with a second layer of a cloaking chemical that prolongs the life of the nanobin and prevents scavenger cells from seeing it. The nanobin technology limits the exposure of normal tissue to the toxic drug as it passes through the bloodstream. When the nanobin gets absorbed by the abnormal, leaky blood vessels of the tumor, the nanoparticles of arsenic are released and trapped inside the tumor cells. "The anti-tumor effects of the arsenic nanobins against clinically aggressive triple negative breast tumors in mice are extremely encouraging," said Vince Cryns, associate professor of medicine and an endocrinologist at Northwestern Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "There's an urgent need to develop new therapies for poor prognosis triple negative breast cancer." Cryns and Tom O'Halloran, director of the Chemistry of Life Processes Institute at Northwestern, are senior authors of a paper on the research, which will be published July 15 in Clinical Cancer Research and featured on the journal cover. Richard Ahn, a student in the medical scientists training program at Northwestern, is lead author. "Everyone said you can't use arsenic for solid tumors," said O'Halloran, also associate director of basic sciences at the Lurie Cancer Center. "That's because they didn't deliver it the right way. This new technology delivered the drug directly to the tumor, maintained its stability and shielded normal cells from the toxicity. That's huge." The nanoparticle technology has great potential for other existing cancer drugs that have been shelved because they are too toxic or excreted too rapidly, Cryns noted. "We can potentially make those drugs more effective against solid tumors by increasing their delivery to the tumor and by shielding normal cells from their toxicity," he said. "This nanotechnology platform has the potential to expand our arsenal of chemotherapy drugs to treat cancer." "Working with both professors O'Halloran and Cryns has enabled us to develop the nanobins and hopefully create a new platform for the effective treatment of triple negative breast cancer," Ahn said. "Having both a basic science mentor and breast cancer mentor is ideal training for me as a future physician-scientist." Looking ahead, the challenge now is to refine and improve the technology. "How do we make it more toxic to cancer cells and less toxic to healthy cells?" asked Cryns, also the director of SUCCEED, a Northwestern Medicine program to improve the quality of life for breast cancer survivors. Northwestern scientists are working on decorating the nanobins with antibodies that recognize markers on tumor cells to increase the drug's uptake by the tumor. They also want to put two or more drugs into the same nanobin and deliver them together to the tumor. "Once you fine-tune this, you could use what would otherwise be a lethal or highly toxic dose of the drug, because a good deal of it will be directly released in the tumor," O'Halloran said. The research was supported by the National Cancer Institute-funded Northwestern University Center of Cancer Nanotechnology Excellence. Northwestern has one of seven such centers in the United States.

Researchers cut years from drug development with nanoscopic bead technology

Fri, 16 Jul 2010 03:34:14 PDT

New research accepted by the Journal of Molecular Recognition confirms that a revolutionary technology developed at Wake Forest University will slash years off the time it takes to develop drugs – bringing vital new treatments to patients much more quickly. Lab-on-Bead uses tiny beads studded with "pins" that match a drug to a disease marker in a single step, so researchers can test an infinite number of possibilities for treatments all at once. When Lab-on-Bead makes a match, it has found a viable treatment for a specific disease – speeding up drug discovery by as much as 10,000 times and cutting out years of testing and re-testing in the laboratory. "It helps the most interesting new drugs work together to stick their heads up above the crowd," said Jed C. Macosko, Ph.D., an associate professor of Physics at Wake Forest and primary inventor of the Lab-on-Bead technology. "Each type of drug has its own molecular barcode. Then, with the help of matching DNA barcodes on each nanoscopic bead, all the drugs of a certain type find their own 'home' bead and work together to make themselves known in our drug discovery process. It's kind of like when Dr. Seuss's Whos down in Whoville all yelled together so that Horton the elephant and all of his friends could hear them." Macosko and Martin Guthold, Ph.D., an associate professor of physics at Wake Forest and the co-inventor of Lab-on-Bead, will work with the biotechnology startup NanoMedica Inc. to test how drug companies will use the new tool. The company has relocated to Winston-Salem from New Jersey; Macosko serves as the company's chief innovation officer and Guthold is its chief science officer. The company has one year to work with the technology to bring it to market or relinquish the rights to the Lab-on-Bead screens millions of chemicals simultaneously using plastic beads so small that 1,000 of them would fit across a human hair. Pharmaceutical companies would use the technology to identify treatments and diagnostics for conditions ranging from cancer to Alzheimer's. One of the targets the research team has focused on is a breast cancer cell called HER2. "We want to find a molecule that detects that cancer cell," Guthold said. "In that circumstance, you could use Lab-on-Bead as a diagnostic tool." The North Carolina Biotechnology Center, a private, nonprofit corporation funded by the N.C. General Assembly, provided $75,000 in funding for the project. Harvard University in Boston and Université de Strasbourg in Strasbourg, France, are providing the chemicals being screened in the Lab-on-Bead process. "There are an infinite number of possibilities for combining carbon, nitrogen, hydrogen and other elements into different shapes that interact differently in the cells," Macosko said. "Those shapes could block cancer – they could block all kinds of things. "If there's some cure to a disease or way to diagnose it, we're going to find it faster."

University of Toronto chemists make breakthrough in nanoscience research

Tue, 13 Jul 2010 03:34:54 PDT

A team of scientists led by Eugenia Kumacheva of the Department of Chemistry at the University of Toronto has discovered a way to predict the organization of nanoparticles in larger forms by treating them much the same as ensembles of molecules formed from standard chemical reactions. "Currently, no model exists describing the organization of nanoparticles," says Kumacheva. "Our work paves the way for the prediction of the properties of nanoparticle ensembles and for the development of new design rules for such structures." The focus of nanoscience is gradually shifting from the synthesis of individual nanoparticles to their organization in larger structures. In order to use nanoparticle ensembles in functional devices such as memory storage devices or optical waveguides, it is important to achieve control of their structure. According to the researchers' observations, the self-organization of nanoparticles is an efficient strategy for producing nanostructures with complex, hierarchical architectures. "The past decade has witnessed great progress in nanoscience – particularly nanoparticle self-assembly – yet the quantitative prediction of the architecture of nanoparticle ensembles and of the kinetics of their formation remains a challenge," she continues. "We report on the remarkable similarity between the self-assembly of metal nanoparticles and chemical reactions leading to the formation of polymer molecules. The nanoparticles act as multifunctional single units, which form reversible, noncovalent bonds at specific bond angles and organize themselves into a highly ordered polymer." "We developed a new approach that enables a quantitative prediction of the architecture of linear, branched, and cyclic self-assembled nanostructures, their aggregation numbers and size distribution, and the formation of structural isomers." Kumacheva was joined in the research by postdoctoral fellows Kun Liu, Nana Zhao and Wei Li, and former doctoral student Zhihong Nie, along with Professor Michael Rubinstein of the University of North Carolina. As polymer chemists, the team took an unconventional look at nanoparticle organization. "We treated them as molecules, not particles, which in a process resembling a polymerization reaction, organize themselves into polymer-like assemblies," says Kumacheva. "Using this analogy, we used the theory of polymerization and predicted the architecture of the so-called 'molecules' and also found other, unexpected features that can find interesting applications."

Researchers use nanoparticles to shrink tumors in mice

Sat, 10 Jul 2010 03:31:07 PDT

The application of nanotechnology in the field of drug delivery has attracted much attention in recent years. In cancer research, nanotechnology holds great promise for the development of targeted, localized delivery of anticancer drugs, in which only cancer cells are affected. Such targeted-therapy methods would represent a major advance over current chemotherapy, in which anticancer drugs are distributed throughout the body, attacking healthy cells along with cancer cells and causing a number of adverse side effects. By carrying out comprehensive studies on mice with human tumors, UCLA scientists have obtained results that move the research one step closer to this goal. In a paper published July 8 in the journal Small, researchers at UCLA's California NanoSystems Institute and Jonsson Comprehensive Cancer Center demonstrate that mesoporous silica nanoparticles (MSNs), tiny particles with thousands of pores, can store and deliver chemotherapeutic drugs in vivo and effectively suppress tumors in mice. The researchers also showed that MSNs accumulate almost exclusively in tumors after administration and that the nanoparticles are excreted from the body after they have delivered their chemotherapeutic drugs. The study was conducted jointly in the laboratories of Fuyu Tamanoi, a UCLA professor of microbiology, immunology and molecular genetics and director of the signal transduction and therapeutics program at UCLA's Jonsson Comprehensive Cancer Center, and Jeffrey Zink, a UCLA professor of chemistry and biochemistry. Tamanoi and Zink are researchers at the California NanoSystems Institute (CNSI) and are two of the co-directors of the CNSI's Nano Machine Center for Targeted Delivery and On-Demand Release. The lead investigator on the research is Jie Lu, a postdoctoral fellow in Tamanoi's lab. Monty Liong and Zongxi Li, researchers from Zink's lab, also contributed to this work. In the study, researchers found that MSNs circulate in the bloodstream for extended periods of time and accumulate predominantly in tumors. The tumor accumulation could be further improved by attaching a targeting moiety to MSNs, the researchers said. The treatment of mice with camptothecin-loaded MSNs led to shrinkage and regression of xenograft tumors. By the end of the treatment, the mice were essentially tumor free, and acute and long-term toxicity of MSNs to the mice was negligible. Mice with breast cancer were used in this study, but the researchers have recently obtained similar results using mice with human pancreatic cancer. "Our present study shows, for the first time, that MSNs are effective for anticancer drug delivery and that the capacity for tumor suppression is significant," Tamanoi said. "Two properties of these nanoparticles are important," Lu said. "First, their ability to accumulate in tumors is excellent. They appear to evade the surveillance mechanism that normally removes materials foreign to the body. Second, most of the nanoparticles that were injected into the mice were excreted out through urine and feces within four days. The latter results are quite interesting and might explain the low toxicity observed in the biocompatabilty experiments we conducted." Researchers at the Nano Machine Center for Targeted Delivery and On-Demand Release are modifying MSNs — which are easily modifiable — so that the nanoparticles can be equipped with nanomachines. For example, nanovalves are being attached at the opening of the pores to control the release of anticancer drugs. In addition, the interior of the pores is being modified so that the light-induced release of anticancer drugs can be achieved. "We can modify both the particles themselves and also the attachments on the particles in a wide variety of ways, which makes this material particularly attractive for engineering drug-delivery vehicles," Zink said. The team is now planning future research that involves testing MSNs in a variety of animal-model systems and carrying out extensive studies on the safety of MSNs. "Comprehensive investigation with practical dosages which are adequate and suitable for in vivo delivery of anticancer drugs is needed before MSNs can reach clinics as a drug-delivery system," Tamanoi said.

Air pollution doesn't increase risk of preeclampsia, early delivery, study finds

Sat, 03 Jul 2010 04:20:47 PDT

While pregnant women may worry about the effects of air pollution on their health and that of their developing child, exposure to carbon monoxide and fine particles in the air during pregnancy does not appear to increase the risk of preterm delivery or preeclampsia -- a serious condition that arises only during pregnancy -- according to results of a study headed by a University at Buffalo epidemiologist. The research was conducted in the region around Seattle, Wash., using data from 3,675 women who were enrolled in the Omega Study, an investigation of the effects of diet and environment on women's health and nutrition before and during pregnancy. Carole Rudra, PhD, assistant professor of social and preventive medicine at UB and first author on the study, presented the results June 23 at the Society for Pediatric and Perinatal Epidemiology annual meeting held in Seattle June 22-23. Rudra studies the ways in which the human-made environment and maternal behaviors affect health during pregnancy. "There is strong evidence that air pollutants may increase risk of cardiovascular disease," says Rudra. "This led me to examine air pollutants in relation to preeclampsia, which is similar to cardiovascular disease and a risk factor for the condition. Pollutants may interfere with delivery of oxygen to the placenta and increase maternal oxidative stress and inflammation. These pathways could lead to both preeclampsia and preterm delivery." Rudra noted that carbon monoxide levels were fairly high in the Seattle area in comparison with other U.S. cities when she began this research, but have declined significantly in recent years. Rudra and colleagues collected data from regional air-pollutant-monitoring reports on concentrations of carbon monoxide (CO) and minute airborne particles (such as dust, fumes, mist, smog and smoke) during specific exposure windows at residences of study participants. The exposure windows were the three months before pregnancy, the total of the first four months of pregnancy, during each trimester and the last month of pregnancy. Preeclampsia is a condition in which high blood pressure and protein in the urine develop after the 20th week (late second or third trimester) of pregnancy. Symptoms are swelling of the hands, face or eyes, and sudden weight gain. Delivery is the only cure. Preterm delivery was defined for this study as occurring less than 37 weeks of gestation. Analysis of the data showed that the amount of air pollutant exposure at any of the collection times had no effect on either of the pregnancy problems. "In this geographic setting and population, these two air pollutant exposures do not appear to increase risks of preeclampsia and preterm delivery," notes Rudra. She now is planning to examine women's health outcomes in relation to air pollutants in Western New York. Michelle A. Williams, PhD, professor of epidemiology and global health at the University of Washington, is principal investigator on the Omega Study and a coauthor on the paper. Lianne Sheppard, PhD, Jane Q. Koenig, PhD, and Melissa A. Schiff, MD, MPH, all from UW, also contributed to the research. The study was funded by the National Institutes of Health. The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.

The ant queen's chemical crown

Thu, 01 Jul 2010 03:19:39 PDT

The defining feature of social insects is that societies contain queens, which specialise in laying eggs, as well as workers, which are mostly infertile but take care of the offspring and the nest. However, when the queen dies or is re-moved, workers begin laying eggs of their own. Previous observations have suggested that queens possess a specific pheromone which keeps the workers infer-tile, but the pheromone has never been identified except in the well-studied honeybee. Queen pheromones have a lot to tell us about how sociality evolved. For example, if the pheromone was found to be brain-washing the workers into doing something that was bad for them, this would suggest that sociality is rife with hidden conflicts. Alternatively, the pheromone might be more like an advertise-ment that demonstrates to the workers that the queen is doing a good job. Workers that can smell that their queen is laying lots of eggs are expected to remain infertile and let the queen do what she does best. After identifying a candidate queen pheromone in the black garden ant, researchers from the Centre for Social Evolution at the University of Copenhagen (Luke Holman, Charlotte Jørgensen, John Nielsen and Patrizia d'Ettorre) made a synthetic copy of the pheromone to definitively test its function. They found that worker ants separated from their queen developed large ovaries in preparation for laying eggs. However, if the orphaned ants were given a glass model queen coated in synthetic queen pheromone, they remained infertile. The authors also found that the queen's eggs are covered in pheromone, and that sick queens pro-duced less pheromone. Together, these results suggest that the queen phero-mone lets the workers know that the queen is laying many eggs and is in good health. The queen pheromones of other social insects, including wasps and ter-mites, remain to be found. More will hopefully be discovered soon, and we will be able to determine whether there are universal queen pheromones, or whether they are highly specific to each species. This will reveal how fast the pheromones evolve and shed light on why specific chemicals became queen pheromones.

UD prof helps discover new chemical method important to drug design, agrichemicals

Mon, 28 Jun 2010 03:32:42 PDT

University of Delaware scientist Donald Watson is part of a research team that has discovered an easier method for incorporating fluorine into organic molecules, giving chemists an important new tool in developing materials ranging from new medicines to agricultural chemicals. The research, which is reported in the June 25 edition of Science, was led by Stephen Buchwald, the Camille Dreyfus Professor of Chemistry at the Massachusetts Institute of Technology. Watson worked in Buchwald's lab at MIT as a postdoctoral research associate prior to joining the UD Department of Chemistry and Biochemistry as an assistant professor this past September. About 25 percent of pharmaceuticals contain fluorine, according to Watson, but it's difficult to incorporate the element into drug molecules. Numerous researchers have been working to develop general methods to introduce fluorine atoms into organic molecules under mild reaction conditions. “The introduction of fluorine atoms into a pharmaceutical compound can have pronounced effects,” Watson notes. “They can modulate the uptake of the drug and stabilize it against metabolism by the body, keeping it in a person's system longer and making it more effective.” The chemical method discovered by the research team uses a soluble palladium (a precious metal) catalyst to replace a chlorine atom in an aromatic molecule with a trifluoromethyl (CF3) group, which contains one carbon and three fluorine atoms. The process is highly general and occurs under mild conditions, and may become even more economical in the future as less expensive reagents are identified, Watson says. Watson's role in the research effort was in early stage development. He dissected the complex chemical process into manageable pieces, isolating the first compounds critical to the reaction and demonstrating their effectiveness. This is the second article in this research field that the team has published in Science during the past year. The work on which the first article is based will result in Watson's first patent, co-authored with colleagues at MIT. Today, in his laboratory at UD, Watson works on developing homogeneous transition metal-based catalysts for use in organic chemistry. He hopes the processes that he is discovering will find use in pharmaceutical, agrichemical, and alternative energy research. His aim is to help build the chemist's toolkit, providing tools -- in the form of chemical reactions -- that other chemists can use to make new molecules. “In my lab we do basic science that has the potential for real-world applications,” Watson says. “We're working with the nuts and bolts, getting to develop stuff that other scientists can use. It's exhilarating to do research that will impact the way chemists build molecules. “Making molecules and new catalysts is exciting,” he adds. “To be able to sketch out a new compound and then make a new substance is a unique experience. It's pretty thrilling to be able to create new substances that other people have never seen before.” Watson has a growing laboratory group, with three graduate students, an undergraduate student, and a laboratory assistant. “They are an incredible group of hard-working and highly talented students, and their science will have an impact,” he says. He knows that the experience in his lab has the potential to transform their lives just as his lab experiences did. As an undergraduate, Watson explains, his interests were torn -- would he pursue physics, chemistry, or chemical engineering? Then as a sophomore in college he got involved in laboratory research in organic chemistry. The opportunity to work on something someone hadn't worked on before hooked him. “I really like having undergraduate and early graduate students in the lab with me now,” Watson notes. “Being able to work with young scientists who are just getting started is very rewarding. I hope that I will be able to show them how exciting and important this field is. Being able to return that favor to others is a great privilege in this job.”

Evidence that nanoparticles in sunscreens could be toxic if accidentally eaten

Thu, 24 Jun 2010 03:23:51 PDT

Scientists are reporting that particle size affects the toxicity of zinc oxide, a material widely used in sunscreens. Particles smaller than 100 nanometers are slightly more toxic to colon cells than conventional zinc oxide. Solid zinc oxide was more toxic than equivalent amounts of soluble zinc, and direct particle to cell contact was required to cause cell death. Their study is in ACS' Chemical Research in Toxicology, a monthly journal. Philip Moos and colleagues note that there is ongoing concern about the potential toxicity of nanoparticles of various materials, which may have different physical and chemical properties than larger particles. Barely 1/50,000 the width of a human hair, nanoparticles are used in foods, cosmetics and other consumer products. Some sunscreens contain nanoparticles of zinc oxide. "Unintended exposure to nano-sized zinc oxide from children accidentally eating sunscreen products is a typical public concern, motivating the study of the effects of nanomaterials in the colon," the scientists note. Their experiments with cell cultures of colon cells compared the effects of zinc oxide nanoparticles to zinc oxide sold as a conventional powder. They found that the nanoparticles were twice as toxic to the cells as the larger particles. Although the nominal particle size was 1,000 times larger, the conventional zinc oxide contained a wide range of particle sizes and included material small enough to be considered as nanoparticles. The concentration of nanoparticles that was toxic to the colon cells was equivalent to eating 2 grams of sunscreen — about 0.1 ounce. This study used isolated cells to study biochemical effects and did not consider the changes to particles during passage through the digestive tract. The scientists say that further research should be done to determine whether zinc nanoparticle toxicity occurs in laboratory animals and people.

Using carbon nanotubes in lithium batteries can dramatically improve energy capacity

Mon, 21 Jun 2010 03:20:14 PDT

Batteries might gain a boost in power capacity as a result of a new finding from researchers at MIT. They found that using carbon nanotubes for one of the battery's electrodes produced a significant increase — up to tenfold — in the amount of power it could deliver from a given weight of material, compared to a conventional lithium-ion battery. Such electrodes might find applications in small portable devices, and with further research might also lead to improved batteries for larger, more power-hungry applications. To produce the powerful new electrode material, the team used a layer-by-layer fabrication method, in which a base material is alternately dipped in solutions containing carbon nanotubes that have been treated with simple organic compounds that give them either a positive or negative net charge. When these layers are alternated on a surface, they bond tightly together because of the complementary charges, making a stable and durable film. The findings, by a team led by Associate Professor of Mechanical Engineering and Materials Science and Engineering Yang Shao-Horn, in collaboration with Bayer Chair Professor of Chemical Engineering Paula Hammond, are reported in a paper published June 20 in the journal Nature Nanotechnology. The lead authors are chemical engineering student Seung Woo Lee PhD '10 and postdoctoral researcher Naoaki Yabuuchi. Batteries, such as the lithium-ion batteries widely used in portable electronics, are made up of three basic components: two electrodes (called the anode, or negative electrode, and the cathode, or positive electrode) separated by an electrolyte, an electrically conductive material through which charged particles, or ions, can move easily. When these batteries are in use, positively charged lithium ions travel across the electrolyte to the cathode, producing an electric current; when they are recharged, an external current causes these ions to move the opposite way, so they become embedded in the spaces in the porous material of the anode. In the new battery electrode, carbon nanotubes — a form of pure carbon in which sheets of carbon atoms are rolled up into tiny tubes — "self-assemble" into a tightly bound structure that is porous at the nanometer scale (billionths of a meter). In addition, the carbon nanotubes have many oxygen groups on their surfaces, which can store a large number of lithium ions; this enables carbon nanotubes for the first time to serve as the positive electrode in lithium batteries, instead of just the negative electrode. This "electrostatic self-assembly" process is important, Hammond explains, because ordinarily carbon nanotubes on a surface tend to clump together in bundles, leaving fewer exposed surfaces to undergo reactions. By incorporating organic molecules on the nanotubes, they assemble in a way that "has a high degree of porosity while having a great number of nanotubes present," she says. Lithium batteries with the new material demonstrate some of the advantages of both capacitors, which can produce very high power outputs in short bursts, and lithium batteries, which can provide lower power steadily for long periods, Lee says. The energy output for a given weight of this new electrode material was shown to be five times greater than for conventional capacitors, and the total power delivery rate was 10 times that of lithium-ion batteries, the team says. This performance can be attributed to good conduction of ions and electrons in the electrode, and efficient lithium storage on the surface of the nanotubes. In addition to their high power output, the carbon nanotube electrodes showed very good stability over time. After 1,000 cycles of charging and discharging a test battery, there was no detectable change in the material's performance. The electrodes the team produced had thicknesses up to a few microns, and the improvements in energy delivery only were seen at high-power output levels. In future work, the team aims to produce thicker electrodes and extend the improved performance to low-power outputs as well, they say. In its present form, the material might have applications for small, portable electronic devices, says Shao-Horn, but if the reported high power capability were demonstrated in a much thicker form — with thicknesses of hundreds of microns rather than just a few — it might eventually be suitable for other applications such as hybrid cars. While the electrode material was produced by alternately dipping a substrate into two different solutions — a relatively time-consuming process — Hammond suggests that the process could be modified by instead spraying the alternate layers onto a moving ribbon of material, a technique now being developed in her lab. This could eventually open the possibility of a continuous manufacturing process that could be scaled up to high volumes for commercial production, and could also be used to produce thicker electrodes with a greater power capacity. "There isn't a real limit" on the potential thickness, Hammond says. "The only limit is the time it takes to make the layers," and the spraying technique can be up to 100 times faster than dipping, she says. Lee says that while carbon nanotubes have been produced in limited quantities so far, a number of companies are currently gearing up for mass production of the material, which could help to make it a viable material for large-scale battery manufacturing.

Carbon dioxide is the missing link to past global climate changes

Fri, 18 Jun 2010 03:38:27 PDT

Increasingly, the Earth's climate appears to be more connected than anyone would have imagined. El Nino, the weather pattern that originates in a patch of the equatorial Pacific, can spawn heat waves and droughts as far away as Africa. Now, a research team led by Brown University has established that the climate in the tropics over at least the last 2.7 million years changed in lockstep with the cyclical spread and retreat of ice sheets thousands of miles away in the Northern Hemisphere. The findings appear to cement the link between the recent Ice Ages and temperature changes in tropical oceans. Based on that new link, the scientists conclude that carbon dioxide has played the lead role in dictating global climate patterns, beginning with the Ice Ages and continuing today. "We think we have the simplest explanation for the link between the Ice Ages and the tropics over that time and the apparent role of carbon dioxide in the intensification of Ice Ages and corresponding changes in the tropics," said Timothy Herbert, professor of geological sciences at Brown and the lead author of the paper in Science. "It certainly supports the idea of global sensitivity of climate to carbon dioxide as the first order of control on global temperature patterns," Herbert added, "but we don't know why. The answer lies in the ocean, we're pretty sure." The research team, including scientists from Luther College in Iowa, Lafayette College in Pennsylvania, and the University of Hong Kong, analyzed cores taken from the seabed at four locations in the tropical oceans: the Arabian Sea, the South China Sea, the eastern Pacific and the equatorial Atlantic Ocean. They decided to zero in on tropical ocean surface temperatures because these vast bodies, which make up roughly half of the world's oceans, in large measure orchestrate the amount of water in the atmosphere and thus rainfall patterns worldwide, as well as the concentration of water vapor, the most prevalent greenhouse gas. Looking at the chemical remains of tiny marine organisms that lived in the sunlit zone of the ocean, the scientists were able to extract the surface temperature for the oceans for the last 3.5 million years, well before the beginning of the Ice Ages. Beginning about 2.7 million years ago, the geologists found that tropical ocean surface temperatures dropped by 1 to 3 degrees Celsius (1.8 to 5.4 degrees Fahrenheit) during each Ice Age, when ice sheets spread in the Northern Hemisphere and significantly cooled oceans in the northern latitudes. Even more compelling, the tropics also changed when Ice Age cycles switched from roughly 41,000-year to 100,000-year intervals. "The tropics are reproducing this pattern both in the cooling that accompanies the glaciation in the Northern Hemisphere and the timing of those changes," Herbert said. "The biggest surprise to us was how similar the patterns looked all across the tropics since about 2.7 million years ago. We didn't expect such similarity." Climate scientists have a record of carbon dioxide levels for the last 800,000 years — spanning the last seven Ice Ages — from ice cores taken in Antarctica. They have deduced that carbon dioxide levels in the atmosphere fell by about 30 percent during each cycle, and that most of that carbon dioxide was absorbed by high-latitude oceans such as the North Atlantic and the Southern Ocean. According to the new findings, this pattern began 2.7 million years ago, and the amount of atmospheric carbon dioxide absorbed by the oceans has intensified with each successive Ice Age. Geologists know the Ice Ages have gotten progressively colder — leading to larger ice sheets — because they have found debris on the seabed of the North Atlantic and North Pacific left by icebergs that broke from the land-bound sheets. "It seems likely that changes in carbon dioxide were the most important reason why tropical temperatures changed, along with the water vapor feedback," Herbert said. Herbert acknowledges that the team's findings leave important questions. One is why carbon dioxide began to play a major role when the Ice Ages began 2.7 million years ago. Also left unanswered is why carbon dioxide appears to have magnified the intensity of successive Ice Ages from the beginning of the cycles to the present. The researchers do not understand why the timing of the Ice Age cycles shifted from roughly 41,000-year to 100,000-year intervals.

Nanoparticle scientist speaks on new discoveries at Goldschmidt Conference

Wed, 16 Jun 2010 03:19:19 PDT

Scientists who work at the atomic and molecular levels – nanoscale – have to think big. After all, it is at this level where everything happens. Alexandra Navrotsky, Distinguished Professor at the University of California, Davis, and Director of its Nanomaterials in the Environment, Agriculture, and Technology Organized Research Unit, has studied the properties of nanoparticles throughout her career. She presented her findings today in Knoxville, Tenn., at the Goldschmidt Conference, hosted by the University of Tennessee, Knoxville, and Oak Ridge National Laboratory. "Nanoparticles are everywhere. You eat them, drink them, breathe them, pay to have them, and pay even more to get rid of them," Navrotsky said. Nanomaterials science deals with particles that are about one billionth of a meter long. During the conference, Navrotsky spoke on recent discoveries she and Ph.D. student Chengcheng Ma made on the thermodynamic properties of transition metal oxides such as insulators and superconductors. Navrotsky's research group found that the thermodynamic driving force -- the energy needed for oxidized reactions -- depends strongly on particle size. The ease with which these materials change their oxidation state is important in all kinds of applications, for example, the catalytic splitting of water for the production of hydrogen and oxygen, the metabolism of microorganisms and the evolution of mineral deposits. Since chemical and biological reactions occur on the surface of a particle, these activities are enhanced at the nanoparticle scale. An understanding of the way nanoparticles react under certain temperatures and other conditions can be applied to many areas of science, including communication technology; agricultural technology; environmental remediation; interactions in the oceans, atmosphere, and biosphere; and biotechnology for medicine and health. For example, the thermodynamics at the nanoscale in a battery affects its voltage output, so understanding this principle can help scientists make a more efficient battery.

High yield crops keep carbon emissions low

Tue, 15 Jun 2010 03:22:35 PDT

The Green Revolution of the late 20th century increased crop yields worldwide and helped feed an expanding global population. According to a new report published in the Proceedings of the National Academy of Sciences, it also has helped keep greenhouse gas emissions at bay. The researchers estimate that since 1961 higher yields per acre have avoided the release of nearly 600 billion tons of carbon dioxide to the atmosphere. "That's about 20 years of fossil fuel burning at present rates," says study co-author Steven Davis of the Carnegie Institution's Department of Global Ecology. "Our results dispel the notion that industrial agricultural with its petrochemicals are inherently worse for the climate than a more 'old-fashioned' way of doing things." Agriculture is a major source of greenhouse gases. The high-yield crop varieties developed during the Green Revolution produced a bounty of food, but they also increased agriculture's reliance on pesticides, fertilizers, and mechanization. The research team, which also included lead author Jennifer Burney and David Lobell of Stanford University, investigated the net effect of Green Revolution crops on greenhouse gas emissions during the period between 1961 and 2005. They found that although the various inputs to modern farms require more energy and greenhouse gas emissions per unit of food output than did the lower-input methods of the past, crop yields have increased by 135%, reducing the amount of cropland needed to produce the same amount of food. Without these advances, the conversion of vast natural areas to agriculture would have caused much more greenhouse gas emissions—the equivalent of nearly 600 billion tons of CO2 since 1961. "Converting a forest or some scrubland to an agricultural area causes a lot of natural carbon in that ecosystem to be oxidized and lost to the atmosphere" says Davis ."What our study shows is that these indirect impacts from converting land to agriculture outweigh the direct emissions that come from the modern, intensive style of agriculture." The researchers also calculated the benefits of investing in agricultural research as a strategy for reducing greenhouse gas emissions. They estimate that since 1961 agricultural research has averted carbon dioxide emissions at a cost of about $4 per ton of CO2. The potential for emissions reduction compares favorably with other strategies. Agricultural advances have prevented about 13 billion tons of carbon dioxide emissions each year, much more than the estimated 1.8 billion tons obtainable by improvements in energy supply or the estimated 1.7 billion from improved transportation systems. "Agricultural research is one of the cheapest ways of preventing greenhouse gas emissions," says Davis. "And if the past few decades are a guide, it is also a large source of potential reduction."

New research into the deep ocean floor yields promising results for microbiologists

Mon, 14 Jun 2010 03:11:35 PDT

Research by a small group of microbiologists is revealing how marine microbes live in a mysterious area of the Earth: the realm just beneath the deep ocean floor. The ocean crust may be the largest biological reservoir on our planet. Beth Orcutt, a post-doctoral fellow at Aarhus University in Denmark and the University of Southern California, presented her new findings about this little researched realm today at Goldschmidt 2010, an annual conference sponsored by a number of international geochemical societies and hosted this year by the University of Tennessee, Knoxville, and Oak Ridge National Laboratory. "I think this research is exciting because it offers us a glimpse into a habitat on Earth that we know next to nothing about," Orcutt said. "If you consider how much ocean crust there is on Earth, and how much of that is hydrologically active, then this environment could be one of the most massive habitats for microbial life on Earth. There may be new species of life and new types of metabolism that we haven't discovered yet." There has been limited research into this deep marine crust, so Orcutt and her colleagues have developed new hole-boring technologies to study microbial life living beneath rock on the seafloor. Orcutt must use a robotic submarine to reach this realm, buried under 2660 meters (1⅔ miles) of water. Then she must drill through 260 meters (850 feet) of sediment. The microbes Orcutt and her team study receive no light that far beneath the ocean floor, so part of what they are exploring is how these microscopic organisms survive in such harsh conditions. Orcutt believes this research also can yield a new understanding of the potential for life on other planets. The subsurface under deep oceans is an extreme environment for any life to exist. Such environments may be present on other planets, so Orcutt theorizes that life might exist there in the form of microbial organisms. "I hope that the general public will understand that the ocean isn't just a giant pond with a featureless, unexciting bottom," Orcutt said. "The seafloor and sub-seafloor are exciting environments where microbes rule. We have to develop sophisticated experiments to try to learn more about these microbial habitats, experiments which will reveal new information about how life survives and thrives on Earth and maybe about how life may exist on other planets."

New strain of bacteria discovered that could aid in oil spill, other environmental cleanup

Sat, 12 Jun 2010 03:51:03 PDT

Researchers have discovered a new strain of bacteria that can produce non-toxic, comparatively inexpensive “rhamnolipids,” and effectively help degrade polycyclic aromatic hydrocarbons, or PAHs – environmental pollutants that are one of the most harmful aspects of oil spills. Because of its unique characteristics, this new bacterial strain could be of considerable value in the long-term cleanup of the massive Gulf Coast oil spill, scientists say. More research to further reduce costs and scale up production would be needed before its commercial use, they added. The findings on this new bacterial strain that degrades the PAHs in oil and other hydrocarbons were just published in a professional journal, Biotechnology Advances, by researchers from Oregon State University and two collaborating universities in China. OSU is filing for a patent on the discovery. “PAHs are a widespread group of toxic, carcinogenic and mutagenic compounds, but also one of the biggest concerns about oil spills,” said Xihou Yin, a research assistant professor in the OSU College of Pharmacy. “Some of the most toxic aspects of oil to fish, wildlife and humans are from PAHs,” Yin said. “They can cause cancer, suppress immune system function, cause reproductive problems, nervous system effects and other health issues. This particular strain of bacteria appears to break up and degrade PAHs better than other approaches we have available.” The discovery is strain “NY3” of a common bacteria that has been known of for decades, called Pseudomonas aeruginosa. It was isolated from a site in Shaanxi Province in China, where soils had been contaminated by oil. P. aeruginosa is widespread in the environment and can cause serious infections, but usually in people with health problems or compromised immune systems. However, some strains also have useful properties, including the ability to produce a group of “biosurfactants” called rhamnolipids. A “surfactant,” technically, is a type of wetting agent that lowers surface tension between liquids – but we recognize surfactants more commonly in such products as dishwashing detergent or shampoo. Biosurfactants are produced by living cells such as bacteria, fungi and yeast, and are generally non-toxic, environmentally benign and biodegradable. By comparison, chemical surfactants, which are usually derived from petroleum, are commonly toxic to health and ecosystems, and resist complete degradation. Biosurfactants of various types are already used in a wide range of applications, from food processing to productions of paints, cosmetics, household products and pharmaceuticals. But they also have uses in decontamination of water and soils, with abilities to degrade such toxic compounds as heavy metals, carcinogenic pesticides and hydrocarbons. Although the type of biosurfactant called “rhamnolipids” have been used for many years, the newly discovered strain, NY3, stands out for some important reasons. Researchers said in the new study that it has an “extraordinary capacity” to produce rhamnolipids that could help break down oil, and then degrade some of its most serious toxic compounds, the PAHs. Rhamnolipids are not toxic to microbial flora, human beings and animals, and they are completely biodegradable. These are compelling advantages over their synthetic chemical counterparts made from petroleum. Even at a very low concentration, rhamnolipids could remarkably increase the mobility, solubility and bioavailability of PAHs, and strain NY3 of P. aeruginosa has a strong capability of then degrading and decontaminating the PAHs. “The real bottleneck to replacing synthetic chemicals with biosurfactants like rhamnolipid is the high cost of production,” Yin said. “Most of the strains of P. aeruginosa now being used have a low yield of rhamnolipid. But strain NY3 has been optimized to produce a very high yield of 12 grams per liter, from initial production levels of 20 milligrams per liter.” By using low-cost sources of carbon or genetic engineering techniques, it may be possible to reduce costs even further and scale up production at very cost-effective levels, researchers said. The rhamnolipids produced by NY3 strain appear to be stable in a wide range of temperature, pH and salinity conditions, and strain NY3 aggressively and efficiently degrades at least five PAH compounds of concern, the study showed. It’s easy to grow and cultivate in many routine laboratory media, and might be available for commercial use in a fairly short time. Further support to develop the technology is going to be sought from the National Science Foundation. “Compared to their chemically synthesized counterparts, microbial surfactants show great potential for useful activity with less environmental risk,” the researchers wrote in their report. “The search for safe and efficient methods to remove environmental pollutants is a major impetus in the search for novel biosurfactant-producing and PAH-degrading microorganisms.” Collaborating on this research were scientists from Xi’an University of Architecture and Technology and Nanjing Agricultural University in China.

Compound enhances cancer-killing properties of agent in trials

Thu, 10 Jun 2010 03:13:15 PDT

Adding a second agent may make a new, experimental anti-cancer drug effective against a wide range of cancers, researchers at the University of Illinois at Chicago College of Medicine have found. A man-made compound called ARC was shown by UIC researchers in 2006 to cause tumor cells to die while leaving normal cells unharmed. ARC, an acronym for its long chemical name, resembles one of the chemical building blocks of DNA. Andrei Gartel, associate professor of molecular genetics, and coworkers found it by screening more than 2,000 compounds for their ability to inhibit a key step in the cell cycle. Now Gartel's laboratory has found that adding ARC may greatly broaden the activity of an anti-cancer agent from Abbott Laboratories that is currently in FDA trials, making it effective in killing a wide range of cancer types. The results are published online in the journal Molecular Cancer Therapeutics. In the earlier study, ARC was able to induce apoptosis, or cell suicide, in cancer cells, and only did so to a much lesser extent in normal cells, said Gartel, who is also principal author on the new study. ARC works mainly by targeting MCL-1, a member of the Bcl-2 family of cellular molecules, which protect cancer cells from the apoptosis induced by anti-cancer drugs. Gartel and his colleagues were interested in whether ARC might be able to improve the activity of Abbott's investigational drug ABT-737, which inhibits several other members of the Bcl-2 family, but not MCL-1. ABT-737 alone is effective against some small-cell lung cancer cell lines and leukemia cells, but ineffective against other cancer cells, including renal and prostate cancer cell lines. Gartel and his colleagues knew from other research that because MCL-1 has a protective effect, preventing apoptosis, ABT-737 was not effective in cancer cells with active MCL-1. They decided to see if ARC, which inactivates MCL-1, could work together with ABT-737 to kill a wider range of cancer cells. "We found that we could use much smaller concentrations of both agents together and effectively target and kill a broad range of cancer cell lines," said Gartel. "This combination of agents shows tremendous synergy." Reducing the dose can lessen side-effects of potential therapies, Gartel said. The new study suggests that ARC may have potential as an anti-cancer agent in combination therapies with ABT-737, targeting an important cellular pathway, Gartel said.

Researchers capture first images of sub-nano pore structures

Wed, 09 Jun 2010 03:41:02 PDT

Moore's law marches on: In the quest for faster and cheaper computers, scientists have imaged pore structures in insulation material at sub-nanometer scale for the first time. Understanding these structures could substantially enhance computer performance and power usage of integrated circuits, say Semiconductor Research Corporation (SRC) and Cornell University scientists. To help maintain the ever-increasing power and performance benefits of semiconductors – like the speed and memory trend described in Moore's law – the industry has introduced very porous, low-dielectric constant materials to replace silicon dioxide as the insulator between nano-scaled copper wires. This has sped up the electrical signals sent along these copper wires inside a computer chip, and at the same time reduced power consumption. "Knowing how many of the molecule-sized voids in the carefully-engineered Swiss cheese survive in an actual device will greatly affect future designs of integrated circuits," said David Muller, Cornell University professor of applied and engineering physics, and co-director of Kavli Institute for Nanoscale Science at Cornell. "The techniques we developed look deeply, as well as in and around the structures, to give a much clearer picture so complex processing and integration issues can be addressed." The scientists understand that the detailed structure and connectivity of these nanopores have profound control on the mechanical strength, chemical stability and reliability of these dielectrics. With today's announcement, researches now have a nearly atomic understanding of the three-dimensional pore structures of low-k materials required to solve these problems. Welcome to the atomic world: SRC and Cornell researchers were able to devise a method to obtain 3-D images of the pores using electron tomography, leverages imaging advances used for CT scans and MRIs in the medical field, says Scott List, director of interconnect and packaging sciences at SRC, at Research Triangle Park, N.C. "Sophisticated software extracts 3-D images from a series of 2-D images taken at multiple angles. A 2-D picture is worth a thousand words, but a 3-D image at near atomic resolution gives the semiconductor industry new insights into scaling low-k materials for several additional technology nodes."

Bacteria from hot springs reveal clues to evolution of early life and to unlock biofuels' potential

Wed, 09 Jun 2010 03:26:33 PDT

A bacteria that lives in hot springs in Japan may help solve one of the mysteries of the early evolution of complex organisms, according to a study publishing next week in PLoS Biology. It may also be the key to 21st century biofuel production. Biochemists Alan Lambowitz and Georg Mohr began investigating Thermosynechococcus elongatus, a cyanobacterium that can survive at temperatures up to 150 degrees Fahrenheit, after they noticed an unusually high percentage of the bacteria's genetic sequence was composed of elements known as group II introns. "Introns are mysterious elements in evolution," says Lambowitz, a professor of molecular biology and director of the Institute of Molecular and Cellular Biology. "Until the 1970s it was believed that genes in all organisms would be continuous and that they would make a continuous RNA, which would then get translated into a continuous protein. It was found, however, that most genes of the eukaryotes, the higher organisms including humans, aren't like that at all. Most of the genes in higher organism are discontinuous. They consist of DNA coding regions that are separated by areas known as introns. "Genomes become loaded down with these introns, which are thought to have evolved from genomic parasites that existed for their own benefit and could spread without killing the host organism," says Lambowitz. "It remains a major question in evolution as to why these introns exist, and how they came to compose such a large part of the human genome." In order to better understand the early history of introns, Lambowitz and Mohr have focused their investigation on bacteria because they're believed to be the original evolutionary wellspring of the introns. They're looking at T. elongatus in particular because it's the only known bacteria in which introns have proliferated in a manner similar to that in higher organisms, such as humans. "We can't go back a billion years in a time machine to see how introns proliferated in the early eukaryotes," says Mohr, a research scientist in Lambowitz's lab. "What we can do is investigate the mechanisms that have allowed introns to proliferate in this organism, and try to infer how they evolved in eukaryotes, like humans, in which as much as 40 percent of the genome is made up of introns." Among the mechanisms they've identified, perhaps the most surprising has been that heat plays a significant role in allowing introns to proliferate in T. elongatus. High temperatures, like those found in the hot springs in which the bacteria live, can unwind the DNA strands in the genome and make it easier for the introns to insert themselves. This evidence of "DNA melting," says Lambowitz, is particularly suggestive when trying to imagine how introns proliferated in early eukaryotes, because the earth was hotter a billion or so years ago, when the early eukaryotes emerged. The genomes of the early eukaryotes may have begun with only a few introns, but over time, thanks in part to the high temperatures, the introns could have proliferated rapidly. Lambowitz and Mohr's investigation of introns in T. elongatus may also, unexpectedly, prove an enormous boon to researchers who are trying to use other high-temperature ("thermophilic") bacteria to improve the efficiency of biofuels. "There's one bacterial species in particular," says Lambowitz, "which lives at high temperature and is very good at converting cellulose to ethanol, but has been intractable to genetic manipulation. The Department of Energy has a considerable amount of money invested in it, and they need to improve the strains but haven't been able to do it. When we discovered these thermophilic introns, which work better at high temperatures, we were able to adapt them pretty rapidly for gene targeting." The technology for using group II introns in gene targeting, known as targetron technology, was pioneered by Lambowitz and his coworkers. Lambowitz and Mohr are already working with scientists at Oak Ridge National Laboratory to see if they can successfully genetically engineer thermophilic bacteria for increased biofuel production. They also foresee applying what they've discovered about T. elongatus introns and temperature to a whole range of biotech and biomedical applications that involve organisms and enzymes that function best at high temperatures. However, they are still planning to delve further into the more profound, basic scientific questions that drew them to the subject in the first place.

Testing predictions in electrochemical nanosystems

Mon, 07 Jun 2010 03:31:33 PDT

Physicists at the Technische Universitaet Muenchen (TUM) are gearing up for experimental tests of findings they arrived at through theoretical considerations: that electrochemical reactions take place more rapidly on isolated, nanometer-scale electrodes than on their familiar macroscopic counterparts, and that this surprising behavior is caused by thermal noise. Prof. Katharina Krischer and Dr. Vladimir Garcia-Morales published their results earlier this year in the Proceedings of the National Academy of Sciences (PNAS). The project is supported by the TUM Institute for Advanced Study, which emphasizes scientifically "risky" research that may have potential for creating new fields of technology. Familiar processes take unfamiliar turns when they're observed on the nanoscale, where models that accurately describe macroscopic phenomena may not be reliable, or even applicable. Electrochemical reactions, for example, which normally appear to proceed smoothly, seem to halt and stumble in the nanoworld. When the electrodes involved are less than ten nanometers wide, chance plays a bigger role: Random movement of molecules makes the exact timing of reactions unpredictable. Now, however, just such a process can be described by a theoretical model developed by the TUM physicists. They demonstrated their method in a study of nanoscale reactions, published in PNAS, which presented a new electrochemical "master equation" underlying the model. Their results show that thermal noise -- that is, the randomness of molecular movement and individual electron-transfer reactions -- actually plays a constructive role in a nanoscale electrochemical system, enhancing reaction rates. "The effect predicted is robust," says Dr. Vladimir Garcia-Morales, recently named a Carl von Linde Junior Fellow of the TUM Institute for Advanced Study, "and it should show up in many experimental situations." To see for themselves, the researchers have turned their attention from the chalkboard and the computer to the lab bench. Their experiments present several technical challenges. One is not only to fabricate disk-shaped electrodes with a radius of just three to ten nanometers, but also to determine the electrode area accurately. Another tough requirement is setting up the electronics to minimize noise from external sources, to make sure the influence of internal, molecular noise can be observed. "An important aspect," Dr. Garcia-Morales says, "is that the reported effect can change our view on the collective properties of many electrodes. Common intuition suggests that if one makes the electrode area ten times as large, the current would be ten times as high. But, as we show with our theory, the proportionality does not hold any more when the electrode dimension becomes as small as a few nanometers." Experimental validation could also help to transpose the TUM researchers' theory to a variety of situations. They say their method accounts for effects that macroscopic models can't explain and could prove useful in addressing a variety of research questions. "The applicability of the electrochemical master equation is in fact beyond the specific problem addressed in the publication," Prof. Katharina Krischer stresses. "It establishes a general framework for stochastic processes involving electron-transfer reactions. For example, we now use it to predict the quality of electrochemical clocks at the nanoscale."

Nanosponge drug delivery system more effective than direct injection

Thu, 03 Jun 2010 03:44:12 PDT

When loaded with an anticancer drug, a delivery system based on a novel material called nanosponge is three to five times more effective at reducing tumor growth than direct injection. That is the conclusion of a paper published in the June 1 issue of the journal Cancer Research. "Effective targeted drug delivery systems have been a dream for a long time now but it has been largely frustrated by the complex chemistry that is involved," says Eva Harth, assistant professor of chemistry at Vanderbilt, who developed the nanosponge delivery system. "We have taken a significant step toward overcoming these obstacles." The study was a collaboration between Harth's laboratory and that of Dennis E. Hallahan, a former professor of radiation oncology at Vanderbilt who is now at the Washington University School of Medicine. Corresponding authors are Harth and Roberto Diaz at Emory University, who was working in the Hallahan laboratory when the studies were done. To visualize Harth's delivery system, imagine making tiny sponges that are about the size of a virus, filling them with a drug and attaching special chemical "linkers" that bond preferentially to a feature found only on the surface of tumor cells and then injecting them into the body. The tiny sponges circulate around the body until they encounter the surface of a tumor cell where they stick on the surface (or are sucked into the cell) and begin releasing their potent cargo in a controllable and predictable fashion. Targeted delivery systems of this type have several basic advantages: Because the drug is released at the tumor instead of circulating widely through the body, it should be more effective for a given dosage. It should also have fewer harmful side effects because smaller amounts of the drug come into contact with healthy tissue. "We call the material nanosponge, but it is really more like a three-dimensional network or scaffold," says Harth. The backbone is a long length of polyester. It is mixed in solution with small molecules called cross-linkers that act like tiny grappling hooks to fasten different parts of the polymer together. The net effect is to form spherically shaped particles filled with cavities where drug molecules can be stored. The polyester is biodegradable, so it breaks down gradually in the body. As it does, it releases the drug it is carrying in a predictable fashion. "Predictable release is one of the major advantages of this system compared to other nanoparticle delivery systems under development," says Harth. When they reach their target, many other systems unload most of their drug in a rapid and uncontrollable fashion. This is called the burst effect and makes it difficult to determine effective dosage levels. Another major advantage is that the nanosponge particles are soluble in water. Encapsulating the anti-cancer drug in the nanosponge allows the use of hydrophobic drugs that do not dissolve readily in water. Currently, these drugs must be mixed with another chemical, called an adjuvant reagent, that reduces the efficacy of the drug and can have adverse side-effects. It is also possible to control the size of nanosponge particles. By varying the proportion of cross-linker to polymer, the nanosponge particles can be made larger or smaller. This is important because research has shown that drug delivery systems work best when they are smaller than 100 nanometers, about the depth of the pits on the surface of a compact disc. The nanosponge particles used in the current study were 50 nanometers in size. "The relationship between particle size and the effectiveness of these drug delivery systems is the subject of active investigation," says Harth. The other major advantage of Harth's system is the simple chemistry required. The researchers have developed simple, high-yield "click chemistry" methods for making the nanosponge particles and for attaching the linkers, which are made from peptides, relatively small biological molecules built by linking amino acids. "Many other drug delivery systems require complicated chemistry that will be difficult to scale up for commercial production, but we have continually kept this in mind," Harth says. The targeting peptide used in the animal studies was developed by the Hallahan laboratory, which also tested the system's effectiveness in tumor-bearing mice. The peptide used in the study is one that selectively binds to tumors that have been treated with radiation. The drug used for the animal studies was paclitaxel (the generic name of the drug Taxol) that is used in cancer chemotherapy. The researchers recorded the response of two different tumor types – slow-growing human breast cancer and fast-acting mouse glioma – to single injections. In both cases they found that it increased the death of cancer cells and delayed tumor growth "in a manner superior to know chemotherapy approaches." The next step is to perform an experiment with repeated injections to see if the nanosponge system can stop and reverse tumor growth. Harth is also planning to perform the more comprehensive toxicity studies on her nanoparticle delivery system that are required before it can be used in clinical trials.

Nanoparticle PSA test predicts if prostate cancer will return

Thu, 03 Jun 2010 03:41:51 PDT

Men who have just had their cancerous prostate gland removed have one pressing question for their doctors: Am I cured? But conventional tests haven't been sensitive enough to provide a concrete answer. Current tests that measure the level of protein called PSA (prostate-specific antigen), which signals the presence of cancer, often detect no PSA, only to have cancer return in up to 40 percent of the cases. New research from Northwestern University Feinberg School of Medicine and the University International Institute for Nanotechnology shows that an ultrasensitive PSA test using nanoparticle-based technology (VeriSens™ PSA, Nanosphere, Inc., research-use-only) may be able to definitively predict after surgery if the cancer is cured long term or if it will recur. The new test, which is based upon assays invented at Northwestern in the laboratories of co-principal investigator Chad A. Mirkin, is 300 times more sensitive than currently available commercial tests and can detect a very low level of PSA that indicates the cancer has spread beyond the prostate. The test also may pick up cancer recurrence at a much earlier stage, when secondary treatment is most effective for a patient's survival. "This test may provide early and more accurate answers," said co-principal investigator C. Shad Thaxton, M.D., an assistant professor of urology at Feinberg and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "It detects PSA at levels in the blood that cannot be detected by conventional tests. It may allow physicians to act at the earliest and most sensitive time, which we know will provide the patient with the best chance of long- term survival." This ability to quickly detect very low levels of PSA may enable doctors to diagnose men with prostate cancer recurrence years earlier than is currently possible. Prostate cancer is the second leading cause of cancer death for men in the United States. Not only may the new test more accurately predict the course of the disease, it also gives an early indication of whether secondary treatments, such as radiation and hormone therapy, are working. If not, then doctors can quickly begin alternative treatment and refer patients to clinical trials. The study results will be presented June 2 at the American Urological Association 2010 Annual Meeting. These and the results of other Northwestern PSA studies will be presented at the meeting by Lee Zhao, Dae Kim and Hannah Alphs, urology residents at Feinberg. "These studies suggest that the nanotechnology PSA test might become the preferred postoperative PSA test for men who have been treated with radical prostatectomy," said William Catalona, M.D., professor of urology at Feinberg, a physician at Northwestern Memorial Hospital and director of the clinical prostate cancer program at the Lurie Cancer Center. "It should be especially useful in the early identification of men who would benefit from adjuvant postoperative radiation therapy and those who need postoperative salvage radiation therapy for recurrence." Catalona, a senior investigator on the study, was the first to demonstrate that the PSA test could be used as a screening test for prostate cancer. The study confirms and builds on the previous findings of a 2009 pilot study Thaxton conducted with Mirkin, the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, and other colleagues. PSA is a protein normally secreted out of the prostate cells into the semen in high concentrations. Usually, very little diffuses into the blood stream, and the normal PSA value for men without prostate disease is less than 2 nanograms per milliliter. When the prostate gland has a disease process, such as inflammation, benign enlargement or cancer, the barriers to PSA diffusion into the blood stream are breached, and PSA levels rise. In a man who has his cancerous prostate removed, there should be no PSA in the blood except for a minute amount produced by the periurethral glands. However, any PSA produced by cancer recurrence ends up in the blood stream and can be detected earlier with the more sensitive nanotechnology PSA assay. For the new study, researchers obtained blood serum retrospectively from men whose PSA serum samples had been frozen after surgery and whose assays (blood analysis) showed an undetectable PSA level based on the conventional test. Northwestern researchers then tested those serum samples using the more sensitive nanotechnology-based test. They wanted to see if they could detect PSA at levels below the limit of the conventional test, and if those results could predict the cancer outcome for those patients, who were followed for up to 10 years. Using the new test, Thaxton and colleagues found that the low and non-rising PSA levels (presumably produced by the normal periurethral glands) of patients meant that the prostate cancer was effectively cured and did not return over a period of at least 10 years. Scientists also found a PSA level higher than that expected from the periurethral glands based on the new test meant the patients would have their disease recur. As result of the study, researchers were able to assign a PSA level number to a cure for the first time as well as a number that indicated the disease would recur and if it would recur aggressively. These newly identified levels were below what could have been detected with the conventional PSA test. The researchers were able to quantify PSA values at less than 0.1 nanograms per milliliter, the clinical limit of detection for commercial assays. Thaxton said the next step for scientists is a prospective clinical trial to compare the nanoparticle-enhanced PSA assay to traditional PSA assays and determine if earlier detection and treatment can save lives.

Atmospheric scientists start monthlong air sampling campaign

Thu, 03 Jun 2010 03:28:52 PDT

More than 60 scientists from a dozen institutions have converged on this urban area to study how tiny particles called aerosols affect the climate. Sending airplanes and weather balloons outfitted with instruments up in the air, the team will be sampling aerosols in the Sacramento Valley from June 2-28. Researchers from the Department of Energy's Pacific Northwest National Laboratory in Richland, Washington will be leading the monthlong study, coordinating air and ground operations at three sites in the Central Valley. Participating scientists hail from several DOE national laboratories, NASA and the University of California, Davis, along with many other academic and research institutions. The data they are collecting will help researchers improve computer models that simulate the climate and project climate changes. One of the areas of climate science that researchers know the least about is aerosols, the tiny particles of dust, soot, salts, water and other chemicals suspended in the air. A hazy day? That is mainly caused by aerosol particles scattering and absorbing sunlight. To better understand aerosols' role in climate, the DOE's climate research program studies how aerosol particles in the air scatter and absorb the sun's radiation, and how much of it hits Earth. This Atmospheric Radiation Measurement (ARM) Climate Research Facility study, called the Carbonaceous Aerosols and Radiative Effects Study (CARES), is looking at aerosols that have a bit of black carbon and organic chemicals in them. These can come from vehicle exhaust, fires -- even plants give off carbon-containing compounds that find their way into aerosols. The team of researchers will take daily measurements of trace gases and aerosols the city emits -- known as the Sacramento urban plume -- under relatively well-defined and regular weather conditions. The knowledge gained will eventually be used in regional and global computer models that simulate the effects of aerosols on climate. About half of the researchers will take measurements on the ground at two sites – one at American River College in Sacramento and the other at Northside School in Cool, Calif. The rest of the team will take similar measurements from the air using a full payload of instruments -- some recently purchased with American Recovery and Reinvestment Act funds -- flown on a Gulfstream-1 aircraft at about 1,000 feet. NASA will fly a King Air B-200 above the G-1 at 28,000 feet. In addition, the team will be sending weather balloons up for additional sampling from the ground sites. The simultaneous measurements from ground, plane and balloon will provide a comprehensive view of the atmospheric aerosols.

Revealing the ancient Chinese secret of sticky rice mortar

Mon, 31 May 2010 04:34:01 PDT

Scientists have discovered the secret behind an ancient Chinese super-strong mortar made from sticky rice, the delicious “sweet rice” that is a modern mainstay in Asian dishes. They also concluded that the mortar ― a paste used to bind and fill gaps between bricks, stone blocks and other construction materials ― remains the best available material for restoring ancient buildings. Their article appears in the American Chemical Society (ACS) monthly journal, Accounts of Chemical Research. Bingjian Zhang, Ph.D., and colleagues note that construction workers in ancient China developed sticky rice mortar about 1,500 years ago by mixing sticky rice soup with the standard mortar ingredient. That ingredient is slaked lime, limestone that has been calcined, or heated to a high temperature, and then exposed to water. Sticky rice mortar probably was the world’s first composite mortar, made with both organic and inorganic materials. The mortar was stronger and more resistant to water than pure lime mortar, and what Zhang termed one of the greatest technological innovations of the time. Builders used the material to construct important buildings like tombs, pagodas, and city walls, some of which still exist today. Some of the structures were strong enough to shrug off the effects of modern bulldozers and powerful earthquakes. Their research identified amylopectin, a type of polysaccharide, or complex carbohydrate, found in rice and other starchy foods, as the “secret ingredient” that appears to be responsible for the mortar’s legendary strength. “Analytical study shows that the ancient masonry mortar is a kind of special organic-inorganic composite material,” the scientists explained. ”The inorganic component is calcium carbonate, and the organic component is amylopectin, which comes from the sticky rice soup added to the mortar. Moreover, we found that amylopectin in the mortar acted as an inhibitor: The growth of the calcium carbonate crystal was controlled, and a compact microstructure was produced, which should be the cause of the good performance of this kind of organic-organic mortar.” To determine whether sticky rice can aid in building repair, the scientists prepared lime mortars with varying amounts of sticky rice and tested their performance compared to traditional lime mortar. “The test results of the modeling mortars shows that sticky rice-lime mortar has more stable physical properties, has greater mechanical strength, and is more compatible, which make it a suitable restoration mortar for ancient masonry,” the article notes. The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 161,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

NIST scientists gain new 'core' understanding of nanoparticles

Fri, 28 May 2010 03:17:01 PDT

While attempting to solve one mystery about iron oxide-based nanoparticles, a research team working at the National Institute of Standards and Technology (NIST) stumbled upon another one. But once its implications are understood, their discovery* may give nanotechnologists a new and useful tool. The nanoparticles in question are spheres of magnetite so tiny that a few thousand of them lined up would stretch a hair's width, and they have potential uses both as the basis of better data storage systems and in biological applications such as hyperthermia treatment for cancer. A key to all these applications is a full understanding of how large numbers of the particles interact magnetically with one another across relatively large distances so that scientists can manipulate them with magnetism. "It's been known for a long time that a big chunk of magnetite has greater magnetic 'moment'—think of it as magnetic strength—than an equivalent mass of nanoparticles," says Kathryn Krycka, a researcher at the NIST Center for Neutron Research. "No one really knows why, though. We decided to probe the particles with beams of low-energy neutrons, which can tell you a great deal about a material's internal structure." The team applied a magnetic field to nanocrystals composed of 9 nm-wide particles, made by collaborators at Carnegie Mellon University. The field caused the particles to line up like iron filings on a piece of paper held above a bar magnet. But when the team looked closer using the neutron beam, what they saw revealed a level of complexity never seen before. "When the field is applied, the inner 7 nm-wide 'core' orients itself along the field's north and south poles, just like large iron filings would," Krycka says. "But the outer 1 nm 'shell' of each nanoparticle behaves differently. It also develops a moment, but pointed at right angles to that of the core." In a word, bizarre. But potentially useful. The shells are not physically different than the interiors; without the magnetic field, the distinction vanishes. But once formed, the shells of nearby particles seem to heed one another: A local group of them will have their shells' moments all lined up one way, but then another group's shells will point elsewhere. This finding leads Krycka and her team to believe that there is more to be learned about the role that particle interaction has on determining internal, magnetic nanoparticle structure—perhaps something nanotechnologists can harness. "The effect fundamentally changes how the particles would talk to each other in a data storage setting," Krycka says. "If we can control it—by varying their temperature, for example, as our findings suggest we can—we might be able to turn the effect on and off, which could be useful in real-world applications."

Brown chemists report promising advance in fuel-cell technology

Tue, 25 May 2010 04:02:00 PDT

Creating catalysts that can operate efficiently and last a long time is a big barrier to taking fuel-cell technology from the lab bench to the assembly line. The precious metal platinum has been the choice for many researchers, but platinum has two major downsides: It is expensive, and it breaks down over time in fuel-cell reactions. In a new study, chemists at Brown University report a promising advance. They have created a unique core and shell nanoparticle that uses far less platinum yet performs more efficiently and lasts longer than commercially available pure-platinum catalysts at the cathode end of fuel-cell reactions. The chemistry known as oxygen reduction reaction takes place at the fuel cell’s cathode, creating water as its only waste, rather than the global-warming carbon dioxide produced by internal combustion systems. The cathode is also where up to 40 percent of a fuel cell’s efficiency is lost, so “this is a crucial step in making fuel cells a more competitive technology with internal combustion engines and batteries,” said Shouheng Sun, professor of chemistry at Brown and co-author of the paper in the Journal of the American Chemical Society. The research team, which includes Brown graduate student and co-author Vismadeb Mazumder and researchers from Oak Ridge National Laboratory in Tennessee, created a five-nanometer palladium (Pd) core and encircled it with a shell consisting of iron and platinum (FePt). The trick, Mazumder said, was in molding a shell that would retain its shape and require the smallest amount of platinum to pull off an efficient reaction. The team created the iron-platinum shell by decomposing iron pentacarbonyl [Fe(CO)₅] and reducing platinum acetylacetonate [Pt(acac)₂], a technique Sun first reported in a 2000 Science paper. The result was a shell that uses only 30 percent platinum, although the researchers say they expect they will be able to make thinner shells and use even less platinum........> Full story

New method for producing 'libraries' of important carbohydrate molecules

Mon, 24 May 2010 03:26:07 PDT

Scientists some years back found ways to automate the production of DNA and proteins, making studies of these essential components of life far easier. With complex carbohydrates, it's been a different story. Until now, the construction of so-called "libraries" of carbohydrate molecules for biological study has been slow and tedious. In what may change all that, a team of scientists from the University of Georgia has created a method for the rapid chemical synthesis of complex carbohydrates, and that method could dramatically change the availability of such molecules for research. "In the past, it has simply taken too long to make these molecules, and it has held back progress in the field," said Geert-Jan Boons, Franklin Professor of Chemistry and director of the research. "Now, we have a new method of synthesis that will make well-defined molecules available for in-depth study." The method was reported May 23 in the journal Nature Chemistry. Other authors of the paper, all from UGA when the work was done, include doctoral students Thomas Boltje and Jin Park and postdoctoral associate Jin-Hwan Kim. The team is part of the Complex Carbohydrate Research Center at UGA, and Boons' appointment in chemistry is part of the Franklin College of Arts and Sciences. The work was sponsored by the National Institute of General Medicine Sciences of the National Institutes of Health. "The emerging field of glycomics has been severely hampered by a lack of robust, well-defined libraries of carbohydrate molecules, which are greatly needed to decipher the 'carbohydrate codes' used by cells for processes such as cell signaling, embryogenesis and neuronal development," said Pamela Marino, director of the glycobiology portfolio at the NIH's National Institute of General Medical Sciences. "Dr. Boons has established important new methodology for the rapid synthesis of complex oligosaccharides in a manner amenable to automation, moving the field a step closer to achieving automated synthesis of complex sugars." Glycomics is the study of complete sets of complex carbohydrate structures expressed by specific cells, tissues or organisms. It examines the role of these molecules in areas such as physiology, genetics and disease pathology. The stakes in being able to study and understand the function of oligosaccharides, chains of simple sugars found on the cell surface of all plant and animal cells, are immense. They are involved in such cellular processes as protein folding, the regulation of cell signaling, and fertilization. These complex carbohydrates also are being recognized by pathogens during infection, help control immune cell response and have a role in the development of cancer and autoimmune diseases. The problem is that building carbohydrate chains for biological study has been difficult at best and slow. Unlike DNA, which can be induced to replicate itself millions of times in a laboratory for study, these compounds must be built a molecule at a time, and, even worse, they can be "linked" in different ways, making chemical bonding problematical at best. The problems associated with how to build carbohydrates in the lab go back more than a century. Although there has been, according to the scientists, "tremendous progress" in chemical or enzymatic approaches used to build the compounds, it is "still very time-consuming, and it not uncommon that the preparation of a single, well-defined derivative can take as long as a year." The new method offers the promise of cutting that time to hours because the procedures allow scientists to eliminate intermediate purification steps and will be amenable to automation. "One of the ways to understand the problems we've had is that while DNA and proteins are linear molecules in which the nucleoside or amino acid building blocks are linked together one way, carbohydrates are branched, and they can be linked in two different ways," said Boons. "And it's very hard to control the configuration of these linkages in the laboratory. And that is essential if we are to find ways to build these new libraries of molecules for study." The new method in the Nature Chemistry paper allows researchers to control the configuration of these linkages and install various branching points, making it much easier to synthesize these carbohydrate molecules without intermediate purifications. To see how well the new method works, the team chose the important carbohydrates glucose and galactose to study, and the results for both showed that the method is sound, rapid and potentially important for the construction of complex carbohydrate molecules to study. Further research will confirm that the method will work on other complex carbohydrates, but all indications now are that it will.

Penn-led collaboration mimics library of bio-membranes for use in nanomedicine, drug delivery

Fri, 21 May 2010 04:46:47 PDT

An international collaboration led by chemists and engineers from the University of Pennsylvania has prepared a library of synthetic biomaterials that mimic cellular membranes and that show promise in targeted delivery of cancer drugs, gene therapy, proteins, imaging and diagnostic agents and cosmetics safely to the body in the emerging field called nanomedicine. The study appears in the current issue of the journal Science. The research provides the first description of the preparation, structure, self-assembly and mechanical properties of vesicles and other selected complex nano-assemblies made from Janus dendrimers. The so-called dendrimersomes are stable, bilayer vesicles that spontaneously form from the exact chemical composition of Janus dendrimers. The team reported a myriad of bilayer capsule populations, uniform in size, stable in time in a large variety of media and temperatures, that are tunable by temperature and chemistry with superior mechanical properties to regular liposomes and impermeable to encapsulated compounds. They are capable of incorporating pore-forming proteins, can assemble with structure-directing phospholipids and block copolymers and offer a molecular periphery suitable for chemical functionalization without affecting their self-assembly. Co-authors Virgil Percec of Penn's Department of Chemistry and Daniel A. Hammer of Penn's Department of Bioengineering, joined by Frank Bates and Timothy Lodge of the University of Minnesota, Michael Klein of Temple University and Kari Rissanen of the Jyväskylä University, in Finland, have chemically coupled hydrophilic and hydrophobic dendrons to create amphiphilic Janus dendrimers with a rich palette of morphologies including cubosomes, disks, tubular vesicles and helical ribbons and confirmed the assembled structures using cryogenic transmission electron microscopy and fluorescence microscopy. "Dendrimersomes marry the stability and mechanical strength obtainable from polymersomes, vesicles made from block copolymers, with the biological function of stabilized phospholipid liposomes," said Percec, the P. Roy Vagelos Chair and Professor of Chemistry at Penn, "but with superior uniformity of size, ease of formation and chemical functionalization." "These materials show special promise because their membranes are the thickness of natural bilayer membranes, but they have superior and tunable materials properties," said Hammer, the Alfred G. and Meta A. Ennis Professor of Bioengineering at Penn. "Because of their membrane thickness, it will be more straightforward to incorporate biological components into the vesicle membranes, such as receptors and channels." "No other single class of molecules including block copolymers and lipids is known to assemble in water into such a diversity of supramolecular structures," said Bates, the Regents Professor and Head of the Chemical Engineering and Materials Science Department at the University of Minnesota. Self-assembled nanostructures, obtained from natural and synthetic amphiphiles, increasingly serve as mimics of biological membranes and enable the targeted delivery of drugs, nucleic acids, proteins, gene therapy and imaging agents for diagnostic medicine. The challenge for researchers is creating these precise molecular arrangements that combine to function as safe biological carriers while carrying payload within. Janus dendrimer assemblies offer several advantages to other competing technologies for nano-particle delivery. Liposomes are mimics of cell membranes assembled from natural phospholipids or from synthetic amphiphiles, including polymersomes. But, liposomes are not stable, even at room temperature, and vary widely in size, requiring tedious stabilization and fractionation for all practical applications. Polymersomes, on the other hand, are stable but polydisperse, and most of them are not biocompatible, requiring scientific intervention to combine the best properties of both for nanomedicine. Dendrimersomes offer stability, monodispersity, tenability and versatility, and they significantly advance the science of self-assembled nanostructures for biological and medical applications.

Gene discovery potential key to cost-competitive cellulosic ethanol

Fri, 21 May 2010 04:20:18 PDT

Scientists at the Department of Energy's Oak Ridge National Laboratory are improving strains of microorganisms used to convert cellulosic biomass into ethanol, including a recent modification that could improve the efficiency of the conversion process. Biofuels researchers and industrials have generated improved mutant microorganisms previously, but authors of a paper in the on-line Proceedings of the National Academy of Sciences identify a key Z. mobilis gene for the first time and show the strain's improved efficiency and its potential use for more cost-effective biofuel production. "Microbes have been breaking down plant material to access sugars for millennia, so plants have evolved to have very sophisticated cell structures that make accessing these sugars difficult," said Steven Brown, staff microbiologist in the Biosciences Division and one of the inventors of the improved Z. mobilis strain. Currently, biomass materials like corn stover and switchgrass must undergo a series of pretreatments to loosen the cellular structure enough to extract the sugar cellulose. Brown said these treatments add new challenges because, although they are necessary, they create a range of chemicals known as inhibitors that stall or stop microorganisms like Z. mobilis from performing the fermentation.......> Full story

Particulate air pollution affects heart health

Thu, 20 May 2010 03:28:41 PDT

Breathing polluted air increases stress on the heart's regulation capacity, up to six hours after inhalation of combustion-related small particles called PM2.5, according to Penn State College of Medicine researchers. Stress on the heart from exposure to high levels of PM2.5 may contribute to cardiovascular disease, said Duanping Liao, professor of public health sciences. The body's ability to properly regulate heartbeat so the heart can pump the appropriate amounts of blood into the circulation system relies on the stability of the heart's electrical activity, called electrophysiology. "Air pollution is associated with cardiopulmonary mortality and morbidity, and it is generally accepted that impaired heart electrophysiology is one of the underlying mechanisms," said Fan He, master's program graduate, Department of Public Health Sciences, Penn State College of Medicine. "This impairment is exhibited through fluctuations in the heart rate from beat to beat over an established period of time, known as heart rate variability. It is also exhibited through a longer period for the electric activity to return to the baseline, known as ventricular repolarization. "The time course, how long it would take from exposure to cardiac response, has not been systematically investigated," said He. "We conducted this study to investigate the relationship between particle matter and heart electrophysiology impairment, especially the time course." The researchers published their results in recent issues of the Journal of Exposure Science and Environmental Epidemiology and in Environmental Health Prospective. Liao's team of researchers studied 106 people from central Pennsylvania, mostly in the Harrisburg metropolitan area. Nonsmokers over the age of 45 without severe cardiac problems wore air-quality and heart-rate monitors for 24 hours. The devices recorded data in one-minute intervals. Results indicate that heart electrophysiology was affected up to six hours after elevated PM2.5 exposure. These adverse effects may trigger the onset of acute cardiac events and over time may result in increased risk of chronic heart disease. PM2.5 refers to particles up to 2.5 micrometers in size. Their primary sources are diesel engine and coal combustion outdoors; and oil, gas or wood combustion for cooking and heating indoors. PM2.5 levels are regulated by the U.S. Environmental Protection Agency. "Our findings may contribute to further understanding of the pathophysiology of air pollution-related cardiac events, specifically our results indicating elevated PM2.5 exposure is associated with immediate disturbance of cardiac electrical activities within six hours after exposure," said Liao.

Mysterious ball lightning: Illusion or reality?

Wed, 19 May 2010 03:53:27 PDT

Physicists Josef Peer and Alexander Kendl from the University of Innsbruck have studied electromagnetic fields of different types of lightning strokes occurring during thunderstorms. Their calculations suggest that the magnetic fields of a specific class of long lasting repetitive lightning discharges show the same properties as transcranial magnetic stimulation (TMS), a technique commonly used in clinical and psychiatric practice to stimulate neural activity in the human brain.
Time varying and sufficiently strong magnetic fields induce electrical fields in the brain, specifically, in neurons of the visual cortex, which may invoke phosphenes. “In the clinical application of TMS, luminous and apparently real visual perceptions in varying shapes and colors within the visual field of the patients and test persons are reported and well examined,” says Alexander Kendl. The Innsbruck physicists have now calculated that a near lightning stroke of long lasting thunderbolts may also generate these luminous visions, which are likely to appear as ball lightning. Their findings are published in the journal Physics Letters A........> Full story

Argonne scientists reveal secret of nanoparticle crystallization in real time

Tue, 18 May 2010 03:54:02 PDT

A collaboration between the Advanced Photon Source and Center for Nanoscale Materials at U.S. Department of Energy’s (DOE) Argonne National Laboratory has "seen" the crystallization of nanoparticles in unprecedented detail. “Nanoscience is a hot issue right now, and people are trying to create self-assembled nanoparticle arrays for data and memory storage,” Argonne assistant physicist Zhang Jiang said. “In these devices, the degree of ordering is an important factor.” In order to call up a specific bit of data, it is ideal to store information on a two-dimensional crystal lattice with well-defined graphical coordinates. For example, every bit of information of a song saved on a hard drive must be stored at specific locations, so it can be retrieved later. However, in most cases, defects are inherent in nanoparticle crystal lattices. “Defects in a lattice are like potholes on a road,” Argonne physicist Jin Wang said. “When you’re driving on the highway, you would like to know whether it is going to be a smooth ride or if you will have to zigzag in order to avoid a flat tire. Also, you want to know how the potholes form in the first place, so we can eliminate them.”........> Full story