Could Be Marketing Tool of the Future Is Brain Scans?

Could Be Marketing Tool of the Future Is Brain Scans?

  4:23:00 PM    Science Lover

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Using advanced tools to see the human brain at work, a new generation of marketing experts may be able to test a product's appeal while it is still being designed, according to a new analysis by two researchers at Duke University and Emory University.

PET scan of a normal brain, contemplating snack foods perhaps? 

(Credit: US Department of Health and Human Services, via Wikimedia Commons)

So-called "neuromarketing" takes the tools of modern brain science, like the functional MRI, and applies them to the somewhat abstract likes and dislikes of customer decision-making.

Though this raises the specter of marketers being able to read people's minds (more than they already do), neuromarketing may prove to be an affordable way for marketers to gather information that was previously unobtainable, or that consumers themselves may not even be fully aware of, says Dan Ariely, the James B. Duke professor of psychology and behavioral economics at Duke.

In a perspective piece appearing online in the journal Nature Reviews Neuroscience , Ariely and Gregory S. Berns of Emory's departments of psychiatry, economics and neuropolicy, offer tips on what to look for when hiring a neuromarketing firm, and what ethical considerations there might be for the new field. They also point to some words of caution in interpreting such data to form marketing decisions.

Neuromarketing may never be cheap enough to replace focus groups and other methods used to assess existing products and advertising, but it could have real promise in gauging the conscious and unconscious reactions of consumers in the design phase of such varied products as "food, entertainment, buildings and political candidates," Ariely says.

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Acne Drug Prevents HIV Breakout

Acne Drug Prevents HIV Breakout

  11:54:00 PM    Science Lover

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Johns Hopkins scientists have found that a safe and inexpensive antibiotic in use since the 1970s for treating acne effectively targets infected immune cells in which HIV, the virus that causes AIDS, lies dormant and prevents them from reactivating and replicating.

Janice E. Clements, Ph.D. (Credit: Image courtesy of Johns Hopkins Medical Institutions)

The drug, minocycline, likely will improve on the current treatment regimens of HIV-infected patients if used in combination with a standard drug cocktail known as HAART (Highly Active Antiretroviral Therapy), according to research published now online and appearing in print April 15 in The Journal of Infectious Diseases. "The powerful advantage to using minocycline is that the virus appears less able to develop drug resistance because minocycline targets cellular pathways not viral proteins," says Janice Clements, Ph.D., Mary Wallace Stanton Professor of Faculty Affairs, vice dean for faculty, and professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine.

"The big challenge clinicians deal with now in this country when treating HIV patients is keeping the virus locked in a dormant state," Clements adds. "While HAART is really effective in keeping down active replication, minocycline is another arm of defense against the virus."

Unlike the drugs used in HAART which target the virus, minocycline homes in on, and adjusts T cells, major immune system agents and targets of HIV infection. According to Clements, minocycline reduces the ability of T cells to activate and proliferate, both steps crucial to HIV production and progression toward full blown AIDS.

If taken daily for life, HAART usually can protect people from becoming ill, but it's not a cure. The HIV virus is kept at a low level but isn't ever entirely purged; it stays quietly hidden in some immune cells. If a person stops HAART or misses a dose, the virus can reactivate out of those immune cells and begin to spread.

The idea for using minocycline as an adjunct to HAART resulted when the Hopkins team learned of research by others on rheumatoid arthritis patients showing the anti-inflammatory effects of minocycline on T cells. The Hopkins group connected the dots between that study with previous research of their own showing that minocycline treatment had multiple beneficial effects in monkeys infected with SIV, the primate version of HIV. In monkeys treated with minocycline, the virus load in the cerebrospinal fluid, the viral RNA in the brain and the severity of central nervous system disease were significantly decreased. The drug was also shown to affect T cell activation and proliferation.

"Since minocycline reduced T cell activation, you might think it would have impaired the immune systems in the macaques, which are very similar to humans, but we didn't see any deleterious effect," says Gregory Szeto, a graduate student in the Department of Cellular and Molecular Medicine working in the Retrovirus Laboratory at Hopkins. "This drug strikes a good balance and is ideal for HIV because it targets very specific aspects of immune activation."

The success with the animal model prompted the team to study in test tubes whether minocycline treatment affected latency in human T cells infected with HIV. Using cells from HIV-infected humans on HAART, the team isolated the "resting" immune cells and treated half of them with minocycline. Then they counted how many virus particles were reactivated, finding completely undetectable levels in the treated cells versus detectable levels in the untreated cells.

"Minocycline reduces the capability of the virus to emerge from resting infected T cells," Szeto explains. "It prevents the virus from escaping in the one in a million cells in which it lays dormant in a person on HAART, and since it prevents virus activation it should maintain the level of viral latency or even lower it. That's the goal: Sustaining a latent non-infectious state."

The team used molecular markers to discover that minocycline very selectively interrupts certain specific signaling pathways critical for T cell activation. However, the antibiotic doesn't completely obliterate T cells or diminish their ability to respond to other infections or diseases, which is crucial for individuals with HIV.

"HIV requires T cell activation for efficient replication and reactivation of latent virus," Clement says, "so our new understanding about minocyline's effects on a T cell could help us to find even more drugs that target its signaling pathways."

The research was supported by grants from the National Institutes of Health.

Authors of the paper, in addition to Clements and Szeto, are Angela K. Brice, Sheila A. Barber and Robert F. Siliciano, all of Johns Hopkins. Also, Hung-Chih Yang of National Taiwan University Hospital.

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What Makes You Unique? Not Genes So Much as Surrounding Sequences, Study Finds

What Makes You Unique? Not Genes So Much as Surrounding Sequences, Study Finds

  10:27:00 AM    Science Lover

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The key to human individuality may lie not in our genes, but in the sequences that surround and control them, according to new research by scientists at the Stanford University School of Medicine and Yale University. The interaction of those sequences with a class of key proteins, called transcription factors, can vary significantly between two people and are likely to affect our appearance, our development and even our predisposition to certain diseases, the study found.

Researchers have found that the unique, specific changes among individuals in the sequence of DNA affect the ability of "control proteins" called transcription factors to bind to the regions that control gene expression. (Credit: iStockphoto/Andrey Prokhorov)

The discovery suggests that researchers focusing exclusively on genes to learn what makes people different from one another have been looking in the wrong place.

"We are rapidly entering a time when nearly anyone can have his or her genome sequenced," said Michael Snyder, PhD, professor and chair of genetics at Stanford. "However, the bulk of the differences among individuals are not found in the genes themselves, but in regions we know relatively little about. Now we see that these differences profoundly impact protein binding and gene expression."

Snyder is the senior author of two papers -- one in Science Express and one in Nature -- exploring these protein-binding differences in humans, chimpanzees and yeast. Snyder, the Stanford W. Ascherman, MD, FACS, Professor in Genetics, came to Stanford in July 2009 from Yale, where much of the work was conducted.

Genes, which carry the specific instructions necessary to make proteins do the work of the cell, vary by only about 0.025 percent across all humans. Scientists have spent decades trying to understand how these tiny differences affect who we are and what we become. In contrast, non-coding regions of the genome, which account for approximately 98 percent of our DNA, vary in their sequence by about 1 to 4 percent. But until recently, scientists had little, if any, idea what these regions do and how they contribute to the "special sauce" that makes me, me, and you, you.

Now Snyder and his colleagues have found that the unique, specific changes among individuals in the sequence of DNA affect the ability of "control proteins" called transcription factors to bind to the regions that control gene expression. As a result, the subsequent expression of nearby genes can vary significantly.

"People have done a lot of work over the years to characterize differences in gene expression among individuals," said Snyder. "We're the first to look at differences in transcription-factor binding from person to person." What's more, by selectively breeding, or crossing, yeast strains, Snyder and his colleagues found that many, but not all, of these differences in binding and expression levels are heritable.

In the Science Express paper, which will be published online March 18, Snyder and his colleagues compared the binding patterns of two transcription factors in 10 people and one chimpanzee. They identified more than 15,000 binding sites across the genome for the transcription factor called NF-kB and more than 19,000 sites for another factor called RNA PolII. They then looked to see if every site was bound equally strongly by the proteins, or if there were variations among individuals.

They found that about 25 percent of the PolII sites and 7.5 percent of the NF-kB sites exhibited significant binding differences among individuals -- in some cases greater than two orders of magnitude from one person to another. (For comparison, the binding differences between the humans and the chimpanzee were about 32 percent.) Many of these binding differences could be traced to differences in sequences or structure in the protein binding sites, and several were directly correlated to changes in gene expression levels.

"These binding regions, or chunks, vary among individuals," said Snyder, "and they have a profound impact on gene expression." In particular, the researchers found that several of the variable binding regions were near genes involved in such diseases as type-1 diabetes, lupus, leukemia and schizophrenia.

The researchers confirmed and extended their findings in the Nature paper, which will be published online March 17. In this study, they used yeast to determine that many of the binding differences and variations in gene expression levels in individuals are passed from parent to progeny, and they identify several control proteins that vary -- a study that would have been impossible to perform in humans.

"We conducted the two studies in parallel," said Snyder, "and found the same thing. Many of the binding sites differed. When we mapped the areas of difference, we found that they were associated with key regulators of variation in the population. Together these two studies tell us a lot about the so-called regulatory code that controls variation among individuals."

The research in the Science Express study was supported by the National Institutes of Health, the European Molecular Biology Laboratory and the Howard Hughes Medical Institute's Medical Fellows Program. The research in the Nature study was supported by the National Institutes of Health. In addition to Snyder, other Stanford researchers involved in the two studies include postdoctoral scholars Fabian Grubert, PhD; Minyi Shi, PhD; and Manoj Hariharan, PhD; and graduate student Konrad Karczewski.

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Nano-Based RFID Tags Could Replace Bar Codes

Nano-Based RFID Tags Could Replace Bar Codes

  12:48:00 AM    Science Lover

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Long lines at store checkouts could be history if a new technology created in part at Rice University comes to pass.

RFID tags printed through a new roll-to-roll process could replace bar codes and make checking out of a store a snap. (Credit: Gyou-Jin Cho/Sunchon National University)

Rice researchers, in collaboration with a team led by Gyou-jin Cho at Sunchon National University in Korea, have come up with an inexpensive, printable transmitter that can be invisibly embedded in packaging. It would allow a customer to walk a cart full of groceries or other goods past a scanner on the way to the car; the scanner would read all items in the cart at once, total them up and charge the customer's account while adjusting the store's inventory.

More advanced versions could collect all the information about the contents of a store in an instant, letting a retailer know where every package is at any time.

The technology reported in the March issue of the journal IEEE Transactions on Electron Devices is based on a carbon-nanotube-infused ink for ink-jet printers first developed in the Rice lab of James Tour, the T.T. and W.F. Chao Chair in Chemistry as well as a professor of mechanical engineering and materials science and of computer science. The ink is used to make thin-film transistors, a key element in radio-frequency identification (RFID) tags that can be printed on paper or plastic.

"We are going to a society where RFID is a key player," said Cho, a professor of printed electronics engineering at Sunchon, who expects the technology to mature in five years. Cho and his team are developing the electronics as well as the roll-to-roll printing process that, he said, will bring the cost of printing the tags down to a penny apiece and make them ubiquitous.

RFID tags are almost everywhere already. The tiny electronic transmitters are used to identify and track products and farm animals. They're in passports, library books and devices that let drivers pass through tollbooths without digging for change.

The technology behind RFID goes back to the 1940s, when Léon Theremin, inventor of the self-named electronic music instrument heard in so many '50s science fiction and horror movies, came up with a spy tool for the Soviet Union that drew power from and retransmitted radio waves.

RFID itself came into being in the 1970s and has been widely adopted by the Department of Defense and industry to track shipping containers as they make their way around the world, among many other uses.

But RFID tags to date are largely silicon-based. Paper or plastic tags printed as part of a package would cut costs dramatically. Cho expects his roll-to-roll technique, which uses a gravure process rather than ink-jet printers, to replace the bar codes now festooned on just about everything you can buy.

Cho, Tour and their teams reported in the journal a three-step process to print one-bit tags, including the antenna, electrodes and dielectric layers, on plastic foil. Cho's lab is working on 16-bit tags that would hold a more practical amount of information and be printable on paper as well.

Cho came across Tour's inks while spending a sabbatical at Rice in 2005. "Professor Tour first recommended we use single-walled carbon nanotubes for printing thin-film transistors," Cho said.

Tour's lab continues to support the project in an advisory role and occasionally hosts Cho's students. Tour said Rice owns half of the patent, still pending, upon which all of the technology is based. "Gyou-jin has carried the brunt of this, and it's his sole project," Tour said. "We are advisers and we still send him the raw materials" -- the single-walled carbon nanotubes produced at Rice.

Printable RFIDs are practical because they're passive. The tags power up when hit by radio waves at the right frequency and return the information they contain. "If there's no power source, there's no lifetime limit. When they receive the RF signal, they emit," Tour said.

There are several hurdles to commercialization. First, the device must be reduced to the size of a bar code, about a third the size of the one reported in the paper, Tour said. Second, its range must increase.

"Right now, the emitter has to be pretty close to the tags, but it's getting farther all the time," he said. "The practical distance to have it ring up all the items in your shopping cart is a meter. But the ultimate would be to signal and get immediate response back from every item in your store -- what's on the shelves, their dates, everything.

"At 300 meters, you're set -- you have real-time information on every item in a warehouse. If something falls behind a shelf, you know about it. If a product is about to expire, you know to move it to the front -- or to the bargain bin."

Tour allayed concerns about the fate of nanotubes in packaging. "The amount of nanotubes in an RFID tag is probably less than a picogram. That means you can produce one trillion of them from a gram of nanotubes -- a miniscule amount. Our HiPco reactor produces a gram of nanotubes an hour, and that would be enough to handle every item in every Walmart.

"In fact, more nanotubes occur naturally in the environment, so it's not even fair to say the risk is minimal. It's infinitesimal."

Co-authors of the paper include Rice graduate student Ashley Leonard; Minhun Jung, Jinsoo Noh and Gwangyong Lee of Sunchon National University; and Jaeyoung Kim, Namsoo Lim, Chaemin Lim, Junseok Kim, Kyunghwan Jung and Hwiwon Kang of the Printed Electronics Research Center, Paru Corp., Sunchon, Korea.

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Invisibility cloak created in 3-D

Invisibility cloak created in 3-D

  1:01:00 AM    Science Lover

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Scientists have created the first device to render an object invisible in three dimensions.

The "cloak", described in the journal Science, hid an object from detection using light of wavelengths close to those that are visible to humans.

Previous devices have been able to hide objects from light travelling in only one direction; viewed from any other angle, the object would remain visible.

This is a very early but significant step towards true invisibility cloaks.

Tolga Ergin, a scientist from the Karlsruhe Institute of Technology in Germany led the study.

He told BBC News that his team's cloak was based on the concept that you can "transform space" with a material.

He and his colleagues designed a photonic metamaterial, which influenced the behaviour of light rays.

"You can think of any transformation that you would like to have, and tailor your material to mimic this," he explained.

The basis of the design is known as a "carpet cloak". This was first proposed by Professor Sir John Pendry from Imperial College London, who also took part in this study.

"He proposed the theoretical design of having an object hidden under a bump and making the bump disappear," said Mr Ergin.

"It's like a carpet mirror," he continued. "If you hide an object under it, there is a bump, so you see a distortion in the reflected image.

"We put the carpet cloak on top of that bump and it bends the light so that the distortions disappear.

"You have the impression that the mirror you're looking at is flat."

Bending light

The trick is to change the speed and direction in which light travels through the material - that is, to change the material's refractive index.

The researchers achieved by this using a polymer crystal made up of very tiny rods. "By changing the thickness of the rods, you can change the ratio of air to polymer," explained Dr Ergin.

"Since the refractive index of air is about one and the refractive index of the polymer is about 1.52," he explained, "in principle, we can get any refractive index between those two numbers," he said.

By tailoring the refractive index of the the surface of the bump, the scientists rendered it invisible to a wide range of light wavelengths slightly longer than those that we can see.

As a result, under this light, the reflective surface appeared to be flat.

A similar effect has been achieved previously in two dimensions - changing the refractive index of a piece of silicon by drilling tiny holes in its surface.

But, these holes can only be drilled in one direction.

"So if you at look at the thing from [any other] angles, you immediately see it," said Mr Ergin.

In this case, the team used a technique called laser writing to create their 3-D cloak. This uses a very finely focused laser, to "write" into a light-sensitive material.

"Wherever you put the focus spot into the material, it will harden," explained Dr Ergin. "It's a similar process to photography - when you develop it, whatever hasn't been exposed to the laser will be washed away."

Third dimension

The carpet cloak was originally designed to work in two dimensions. But when Dr Ergin and his colleagues calculated how the rays of light would travel through an object, they realised that they could use their technique to build a structure that would work in three dimensions.

In this case, the researchers use the device to cloak a bump one micrometre (one thousandth of a millimetre) high.

"But in theory there are no limits [to the size of the object you could hide], said Dr Ergin. "You could blow this up and hide a house.

"But it took us three hours to make this structure, so if you wanted to make it even one millimetre in size you would have to wait a very long time."

Professor Ortwin Hess from the University of Surrey in the UK said that this study was a "huge step forward".

"The really remarkable aspect is the demonstration of invisibility in three dimensions."

One of the major challenges that remains in the design of cloaking devices is hiding objects from wavelengths of light that are visible to humans.

"Photonic crystals usually work because the constitutive elements are not visible to the wavelength by which one observes them," Professor Hess explained.

"So if you look at the desk in front of you, you don't see the individual atoms because they are so small. You just see whole structure - the wood or the plastic."

This means that cloaking devices for visible light would have to be made up of much smaller rods. So for this technique, the laser beam would have to be made even smaller.

Currently, the rods can be made as small as 200 nanometres. To hide a bump from visible light would require rods as small as 10 nanometres.

And, as Mr Ergin explained, there is a limit to how small a point light can be focused down to.

"You could say, 'why not just make [the rods] smaller?' but it's not that easy to scale these structures down. Fabrication techniques have their limits," he said.

But Professor Hess said that this was a great achievement and these photonic materials could be used in the development of lenses and in light storage and optical circuitry.

He added: "We won't have a body-sized invisibility cloak tomorrow but this has demonstrated a remarkable proof of principle."

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Advance Boosts Potential for Solar Fuel

Advance Boosts Potential for Solar Fuel

  4:05:00 PM    Science Lover

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Emory University chemists have developed the most potent homogeneous catalyst known for water oxidation, considered a crucial component for generating clean hydrogen fuel using only water and sunlight.

Chemists have developed the most potent homogeneous catalyst known for water oxidation, considered a crucial component for generating clean hydrogen fuel using only water and sunlight. (Credit: Photo by Benjamin Yin, Emory University)

The breakthrough, published March 11 in the journal Science, was made in collaboration with the Paris Institute of Molecular Chemistry.

The fastest, carbon-free molecular water oxidation catalyst (WOC) to date "has really upped the standard from the other known homogeneous WOCs," said Emory inorganic chemist Craig Hill, whose lab led the effort. "It's like a home run compared to a base hit."

In order to be viable, a WOC needs selectivity, stability and speed. Homogeneity is also a desired trait, since it boosts efficiency and makes the WOC easer to study and optimize. The new WOC has all of these qualities, and it is based on the cheap and abundant element cobalt, adding to its potential to help solar energy go mainstream.

Benjamin Yin, an undergraduate student in Hill's lab, is the lead author on the Science paper. Emory chemists who are co-authors include Hill, Yurii Geletii, Jamal Musaev, Zhen Luo and Ken Hardcastle. The U.S. Department of Energy funded the work.

The WOC research is a component of the Emory Bio-inspired Renewable Energy Center, which aims to mimic natural processes such as photosynthesis to generate clean fuel. The next step involves incorporating the WOC into a solar-driven, water-splitting system.

The long-term goal is to use sunlight to split water into oxygen and hydrogen. Hydrogen becomes the fuel. Its combustion produces the by-product of water -- which flows back into a clean, green, renewable cycle.

Three main technical challenges are involved: developing a light collector, a catalyst to oxidize water to oxygen and a catalyst to reduce water to hydrogen. All three components need improvement, but a viable WOC may be the most difficult scientific challenge. "We are aiming for a WOC that is free of organic structure, because organic components will combine with oxygen and self-destruct," Hill says. "You'll wind up with a lot of gunk."

Enzymes are nature's catalysts. The enzyme in the oxygen-evolving center of green plants "is about the least stable catalyst in nature, and one of the shortest lived, because it's doing one of the hardest jobs," Hill says.

"We've duplicated this complex natural process by taking some of the essential features from photosynthesis and using them in a synthetic, carbon-free, homogeneous system. The result is a water oxidation catalyst that is far more stable than the one found in nature."

For decades, scientists have been trying to imitate Mother Nature and create a WOC for artificial photosynthesis. Nearly all of the more than 40 homogeneous WOCs developed by labs have had significant limitations, such as containing organic components that burn up quickly during the water oxidation process.

Two years ago, Hill's lab and collaborators developed the first prototype of a stable, homogenous, carbon-free WOC, which also worked faster than others known at the time. The prototype, however, was based on ruthenium, a relatively rare and expensive element.

Building on that work, the researchers began experimenting with the cheaper and more abundant element cobalt. The cobalt-based WOC has proved even faster than the ruthenium version for light-driven water oxidation.

For more information on sustainable energy research at Emory, go to: http://www.emory.edu/home/news/special/green-energy/

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Frogs, Foam and Fuel: Solar Energy Converted to Sugars

Frogs, Foam and Fuel: Solar Energy Converted to Sugars

  1:14:00 AM    Science Lover

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For decades, farmers have been trying to find ways to get more energy out of the sun. In natural photosynthesis, plants take in solar energy and carbon dioxide and then convert it to oxygen and sugars. The oxygen is released to the air and the sugars are dispersed throughout the plant -- like that sweet corn we look for in the summer. Unfortunately, the allocation of light energy into products we use is not as efficient as we would like. Now engineering researchers at the University of Cincinnati are doing something about that.

In natural photosynthesis, plants take in solar energy and carbon dioxide and then convert it to oxygen and sugars. (Credit: Image courtesy of University of Cincinnati, Illustration by Megan Gundrum, fifth-year DAAP student)

The researchers are finding ways to take energy from the sun and carbon from the air to create new forms of biofuels, thanks to a semi-tropical frog species. Their results have just been published online in Nano Letters.

Research Assistant Professor David Wendell, student Jacob Todd and College of Engineering and Applied Science Dean Carlo Montemagno co-authored the paper, based on research in Montemagno's lab in the Department of Biomedical Engineering. Their work focused on making a new artificial photosynthetic material which uses plant, bacterial, frog and fungal enzymes, trapped within a foam housing, to produce sugars from sunlight and carbon dioxide.

Foam was chosen because it can effectively concentrate the reactants but allow very good light and air penetration. The design was based on the foam nests of a semi-tropical frog called the Tungara frog, which creates very long-lived foams for its developing tadpoles.

"The advantage for our system compared to plants and algae is that all of the captured solar energy is converted to sugars, whereas these organisms must divert a great deal of energy to other functions to maintain life and reproduce," says Wendell. "Our foam also uses no soil, so food production would not be interrupted, and it can be used in highly enriched carbon dioxide environments, like the exhaust from coal-burning power plants, unlike many natural photosynthetic systems."

He adds, "In natural plant systems, too much carbon dioxide shuts down photosynthesis, but ours does not have this limitation due to the bacterial-based photo-capture strategy."

There are many benefits to being able to create a plant-like foam.

"You can convert the sugars into many different things, including ethanol and other biofuels," Wendell explains. "And it removes carbon dioxide from the air, but maintains current arable land for food production."

"This new technology establishes an economical way of harnessing the physiology of living systems by creating a new generation of functional materials that intrinsically incorporates life processes into its structure," says Dean Montemagno. "Specifically in this work it presents a new pathway of harvesting solar energy to produce either oil or food with efficiencies that exceed other biosolar production methodologies. More broadly it establishes a mechanism for incorporating the functionality found in living systems into systems that we engineer and build."

The next step for the team will be to try to make the technology feasible for large-scale applications like carbon capture at coal-burning power plants.

"This involves developing a strategy to extract both the lipid shell of the algae (used for biodiesel) and the cytoplasmic contents (the guts), and reusing these proteins in the foam," says Wendell. "We are also looking into other short carbon molecules we can make by altering the enzyme cocktail in the foam."

Montemagno adds, "It is a significant step in delivering the promise of nanotechnology."

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Nanoparticles: Golden Bullet for Cancer?

Nanoparticles: Golden Bullet for Cancer?

  10:03:00 AM    Science Lover

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In a lecture he delivered in 1906, the German physician Paul Ehrlich coined the term Zuberkugel, or "magic bullet," as shorthand for a highly targeted medical treatment.

Infrared images made while tumors were irradiated with a laser show that in nanocage-injected mice (left), the surface of the tumor quickly became hot enough to kill cells. In buffer-injected mice (right), the temperature barely budged. This specificity is what makes photothermal therapy so attractive as a cancer therapy. (Credit: WUSTL)

Magic bullets, also called silver bullets, because of the folkloric belief that only silver bullets can kill supernatural creatures, remain the goal of drug development efforts today.

A team of scientists at Washington University in St. Louis is currently working on a magic bullet for cancer, a disease whose treatments are notoriously indiscriminate and nonspecific. But their bullets are gold rather than silver. Literally.

The gold bullets are gold nanocages that, when injected, selectively accumulate in tumors. When the tumors are later bathed in laser light, the surrounding tissue is barely warmed, but the nanocages convert light to heat, killing the malignant cells.

In an article just published in the journal Small, the team describes the successful photothermal treatment of tumors in mice.

The team includes Younan Xia, Ph.D., the James M. McKelvey Professor of Biomedical Engineering in the School of Engineering and Applied Science, Michael J. Welch, Ph.D., professor of radiology and developmental biology in the School of Medicine, Jingyi Chen, Ph.D., research assistant professor of biomedical engineering and Charles Glaus, Ph.D., a postdoctoral research associate in the Department of Radiology.

"We saw significant changes in tumor metabolism and histology," says Welch, "which is remarkable given that the work was exploratory, the laser 'dose' had not been maximized, and the tumors were 'passively' rather than 'actively' targeted."

Why the nanocages get hot

The nanocages themselves are harmless. "Gold salts and gold colloids have been used to treat arthritis for more than 100 years," says Welch. "People know what gold does in the body and it's inert, so we hope this is going to be a nontoxic approach."

"The key to photothermal therapy," says Xia, "is the cages' ability to efficiently absorb light and convert it to heat. "

Suspensions of the gold nanocages, which are roughly the same size as a virus particle, are not always yellow, as one would expect, but instead can be any color in the rainbow.

They are colored by something called a surface plasmon resonance. Some of the electrons in the gold are not anchored to individual atoms but instead form a free-floating electron gas, Xia explains. Light falling on these electrons can drive them to oscillate as one. This collective oscillation, the surface plasmon, picks a particular wavelength, or color, out of the incident light, and this determines the color we see.

Medieval artisans made ruby-red stained glass by mixing gold chloride into molten glass, a process that left tiny gold particles suspended in the glass, says Xia.

The resonance -- and the color -- can be tuned over a wide range of wavelengths by altering the thickness of the cages' walls. For biomedical applications, Xia's lab tunes the cages to 800 nanometers, a wavelength that falls in a window of tissue transparency that lies between 750 and 900 nanometers, in the near-infrared part of the spectrum.

Light in this sweet spot can penetrate as deep as several inches in the body (either from the skin or the interior of the gastrointestinal tract or other organ systems).

The conversion of light to heat arises from the same physical effect as the color. The resonance has two parts. At the resonant frequency, light is typically both scattered off the cages and absorbed by them.

By controlling the cages' size, Xia's lab tailors them to achieve maximum absorption.

Passive targeting

"If we put bare nanoparticles into your body," says Xia, "proteins would deposit on the particles, and they would be captured by the immune system and dragged out of the bloodstream into the liver or spleen."

To prevent this, the lab coated the nanocages with a layer of PEG, a nontoxic chemical most people have encountered in the form of the laxatives GoLyTELY or MiraLAX. PEG resists the adsorption of proteins, in effect disguising the nanoparticles so that the immune system cannot recognize them.

Instead of being swept from the bloodstream, the disguised particles circulate long enough to accumulate in tumors.

A growing tumor must develop its own blood supply to prevent its core from being starved of oxygen and nutrients. But tumor vessels are as aberrant as tumor cells. They have irregular diameters and abnormal branching patterns, but most importantly, they have thin, leaky walls.

The cells that line a tumor's blood vessel, normally packed so tightly they form a waterproof barrier, are disorganized and irregularly shaped, and there are gaps between them.

The nanocages infiltrate through those gaps efficiently enough that they turn the surface of the normally pinkish tumor black.

A trial run

In Welch's lab, mice bearing tumors on both flanks were randomly divided into two groups. The mice in one group were injected with the PEG-coated nanocages and those in the other with buffer solution. Several days later the right tumor of each animal was exposed to a diode laser for 10 minutes.

The team employed several different noninvasive imaging techniques to follow the effects of the therapy. (Welch is head of the oncologic imaging research program at the Siteman Cancer Center of Washington University School of Medicine and Barnes-Jewish Hospital and has worked on imaging agents and techniques for many years.)

During irradiation, thermal images of the mice were made with an infrared camera. As is true of cells in other animals that automatically regulate their body temperature, mouse cells function optimally only if the mouse's body temperature remains between 36.5 and 37.5 degrees Celsius (98 to 101 degrees Fahrenheit).

At temperatures above 42 degrees Celsius (107 degrees Fahrenheit) the cells begin to die as the proteins whose proper functioning maintains them begin to unfold.

In the nanocage-injected mice, the skin surface temperature increased rapidly from 32 degrees Celsius to 54 degrees C (129 degrees F).

In the buffer-injected mice, however, the surface temperature remained below 37 degrees Celsius (98.6 degrees Fahrenheit).

To see what effect this heating had on the tumors, the mice were injected with a radioactive tracer incorporated in a molecule similar to glucose, the main energy source in the body. Positron emission and computerized tomography (PET and CT) scans were used to record the concentration of the glucose lookalike in body tissues; the higher the glucose uptake, the greater the metabolic activity.

The tumors of nanocage-injected mice were significantly fainter on the PET scans than those of buffer-injected mice, indicating that many tumor cells were no longer functioning.

The tumors in the nanocage-treated mice were later found to have marked histological signs of cellular damage.

Active targeting

The scientists have just received a five-year, $2,129,873 grant from the National Cancer Institute to continue their work with photothermal therapy.

Despite their results, Xia is dissatisfied with passive targeting. Although the tumors took up enough gold nanocages to give them a black cast, only 6 percent of the injected particles accumulated at the tumor site.

Xia would like that number to be closer to 40 percent so that fewer particles would have to be injected. He plans to attach tailor-made ligands to the nanocages that recognize and lock onto receptors on the surface of the tumor cells.

In addition to designing nanocages that actively target the tumor cells, the team is considering loading the hollow particles with a cancer-fighting drug, so that the tumor would be attacked on two fronts.

But the important achievement, from the point of view of cancer patients, is that any nanocage treatment would be narrowly targeted and thus avoid the side effects patients dread.

The TV and radio character the Lone Ranger used only silver bullets, allegedly to remind himself that life was precious and not to be lightly thrown away. If he still rode today, he might consider swapping silver for gold.

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Psychopaths' Brains Wired to Seek Rewards

Psychopaths' Brains Wired to Seek Rewards

  1:06:00 AM    Science Lover

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The brains of psychopaths appear to be wired to keep seeking a reward at any cost, new research from Vanderbilt University finds. The research uncovers the role of the brain's reward system in psychopathy and opens a new area of study for understanding what drives these individuals.

"Abnormalities in how the nucleus accumbens, highlighted here,processes dopamine have been found in individuals with psychopathic traits and may be linked to violent, criminal behavior."

"This study underscores the importance of neurological research as it relates to behavior," Dr. Francis S. Collins, director of the National Institutes of Health, said. "The findings may help us find new ways to intervene before a personality trait becomes antisocial behavior."

The results were published March 14, 2010, in Nature Neuroscience.

"Psychopaths are often thought of as cold-blooded criminals who take what they want without thinking about consequences," Joshua Buckholtz, a graduate student in the Department of Psychology and lead author of the new study, said. "We found that a hyper-reactive dopamine reward system may be the foundation for some of the most problematic behaviors associated with psychopathy, such as violent crime, recidivism and substance abuse."

Previous research on psychopathy has focused on what these individuals lack -- fear, empathy and interpersonal skills. The new research, however, examines what they have in abundance -- impulsivity, heightened attraction to rewards and risk taking. Importantly, it is these latter traits that are most closely linked with the violent and criminal aspects of psychopathy.

"There has been a long tradition of research on psychopathy that has focused on the lack of sensitivity to punishment and a lack of fear, but those traits are not particularly good predictors of violence or criminal behavior," David Zald, associate professor of psychology and of psychiatry and co-author of the study, said. "Our data is suggesting that something might be happening on the other side of things. These individuals appear to have such a strong draw to reward -- to the carrot -- that it overwhelms the sense of risk or concern about the stick."

To examine the relationship between dopamine and psychopathy, the researchers used positron emission tomography, or PET, imaging of the brain to measure dopamine release, in concert with a functional magnetic imaging, or fMRI, probe of the brain's reward system.

"The really striking thing is with these two very different techniques we saw a very similar pattern -- both were heightened in individuals with psychopathic traits," Zald said.

Study volunteers were given a personality test to determine their level of psychopathic traits. These traits exist on a spectrum, with violent criminals falling at the extreme end of the spectrum. However, a normally functioning person can also have the traits, which include manipulativeness, egocentricity, aggression and risk taking.

In the first portion of the experiment, the researchers gave the volunteers a dose of amphetamine, or speed, and then scanned their brains using PET to view dopamine release in response to the stimulant. Substance abuse has been shown in the past to be associated with alterations in dopamine responses. Psychopathy is strongly associated with substance abuse.

"Our hypothesis was that psychopathic traits are also linked to dysfunction in dopamine reward circuitry," Buckholtz said. "Consistent with what we thought, we found people with high levels of psychopathic traits had almost four times the amount of dopamine released in response to amphetamine."

In the second portion of the experiment, the research subjects were told they would receive a monetary reward for completing a simple task. Their brains were scanned with fMRI while they were performing the task. The researchers found in those individuals with elevated psychopathic traits the dopamine reward area of the brain, the nucleus accumbens, was much more active while they were anticipating the monetary reward than in the other volunteers.

"It may be that because of these exaggerated dopamine responses, once they focus on the chance to get a reward, psychopaths are unable to alter their attention until they get what they're after," Buckholtz said. Added Zald, "It's not just that they don't appreciate the potential threat, but that the anticipation or motivation for reward overwhelms those concerns."

The National Institute on Drug Abuse funded the research.

Zald is an investigator in the Vanderbilt Kennedy Center for Research on Human Development.

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'Waste' Energy Turns Water Into Hydrogen Fuel

'Waste' Energy Turns Water Into Hydrogen Fuel

  11:07:00 PM    Science Lover

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Materials scientists at the University of Wisconsin-Madison have designed a way to harvest small amounts of waste energy and harness them to turn water into usable hydrogen fuel.

A newly developed method harvests small amounts of waste energy and harnesses them to turn water into usable hydrogen fuel. (Credit: iStockphoto/Mustafa Deliormanli)

The process is simple, efficient and recycles otherwise-wasted energy into a useable form.

"This study provides a simple and cost-effective technology for direct water splitting that may generate hydrogen fuels by scavenging energy wastes such as noise or stray vibrations from the environment," the authors write in a new paper, published March 2 in the Journal of Physical Chemistry Letters. "This new discovery may have potential implications in solving the challenging energy and environmental issues that we are facing today and in the future."

The researchers, led by UW-Madison geologist and crystal specialist Huifang Xu, grew nanocrystals of two common crystals, zinc oxide and barium titanate, and placed them in water. When pulsed with ultrasonic vibrations, the nanofibers flexed and catalyzed a chemical reaction to split the water molecules into hydrogen and oxygen.

When the fibers bend, asymmetries in their crystal structures generate positive and negative charges and create an electrical potential. This phenomenon, called the piezoelectric effect, has been well known in certain crystals for more than a century and is the driving force behind quartz clocks and other applications.

Xu and his colleagues applied the same idea to the nanocrystal fibers. "The bulk materials are brittle, but at the nanoscale they are flexible," he says, like the difference between fiberglass and a pane of glass.

Smaller fibers bend more easily than larger crystals and therefore also produce electric charges easily. So far, the researchers have achieved an impressive 18 percent efficiency with the nanocrystals, higher than most experimental energy sources.

In addition, Xu says, "because we can tune the fiber and plate sizes, we can use even small amounts of [mechanical] noise -- like a vibration or water flowing -- to bend the fibers and plates. With this kind of technology, we can scavenge energy waste and convert it into useful chemical energy."

Rather than harvest this electrical energy directly, the scientists took a novel approach and used the energy to break the chemical bonds in water and produce oxygen and hydrogen gas.

"This is a new phenomenon, converting mechanical energy directly to chemical energy," Xu says, calling it a piezoelectrochemical (PZEC) effect.

The chemical energy of hydrogen fuel is more stable than the electric charge, he explains. It is relatively easy to store and will not lose potency over time.

With the right technology, Xu envisions this method being useful for generating small amounts of power from a multitude of small sources -- for example, walking could charge a cell phone or music player and breezes could power streetlights.

"We have limited areas to collect large energy differences, like a waterfall or a big dam," he says. "But we have lots of places with small energies. If we can harvest that energy, it would be tremendous."

The new paper is co-authored by graduate student Kuang-Sheng Hong, research scientist Hiromi Konishi, and mechanical engineering professor Xiaochun Li, all at UW-Madison. Xu's research is supported by grants from the UW-Madison Graduate School, National Science Foundation, NASA Astrobiology Institute and the U.S. Department of Energy.

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