Why Alcohol Is Addicting: Endorphins in Brain

Why Alcohol Is Addicting: Endorphins in Brain

  9:51:00 PM    Science Lover

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Drinking alcohol leads to the release of endorphins in areas of the brain that produce feelings of pleasure and reward, according to a study led by researchers at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco (UCSF).

New research shows that drinking alcohol leads to the
release of endorphins in areas of the brain that produce
feelings of pleasure and reward. (Credit: iStockphoto)

The finding marks the first time that endorphin release in the nucleus accumbens and orbitofrontal cortex in response to alcohol consumption has been directly observed in humans.

Endorphins are small proteins with opiate-like effects that are produced naturally in the brain.

"This is something that we've speculated about for 30 years, based on animal studies, but haven't observed in humans until now," said lead author Jennifer Mitchell, PhD, clinical project director at the Gallo Center and an adjunct assistant professor of neurology at UCSF. "It provides the first direct evidence of how alcohol makes people feel good."

The discovery of the precise locations in the brain where endorphins are released provides a possible target for the development of more effective drugs for the treatment of alcohol abuse, said senior author Howard L. Fields, MD, PhD, a professor of neurology and Endowed Chair in Pharmacology of Addiction in Neurology at UCSF and director of human clinical research at the Gallo Center.

The study appears on January 11, 2012, in Science Translational Medicine.

The researchers used positron emission tomography, or PET imaging, to observe the immediate effects of alcohol in the brains of 13 heavy drinkers and 12 matched "control" subjects who were not heavy drinkers.

In all of the subjects, alcohol intake led to a release of endorphins. And, in all of the subjects, the more endorphins released in the nucleus accumbens, the greater the feelings of pleasure reported by each drinker.

In addition, the more endorphins released in the orbitofrontal cortex, the greater the feelings of intoxication in the heavy drinkers, but not in the control subjects.

"This indicates that the brains of heavy or problem drinkers are changed in a way that makes them more likely to find alcohol pleasant, and may be a clue to how problem drinking develops in the first place," said Mitchell. "That greater feeling of reward might cause them to drink too much."

Results Suggest Possible Approach to Treat Alcohol Abuse

Before drinking, the subjects were given injections of radioactively tagged carfentanil, an opiate-like drug that selectively binds to sites in the brain called opioid receptors, where endorphins also bind. As the radioactive carfentanil was bound and emitted radiation, the receptor sites "lit up" on PET imaging, allowing the researchers to map their exact locations.

The subjects were then each given a drink of alcohol, followed by a second injection of radioactive carfentanil, and scanned again with PET imaging. As the natural endorphins released by drinking were bound to the opioid receptor sites, they prevented the carfentanil from being bound. By comparing areas of radioactivity in the first and second PET images, the researchers were able to map the exact locations -- areas of lower radioactivity -- where endorphins were released in response to drinking.

The researchers found that endorphins released in response to drinking bind to a specific type of opioid receptor, the Mu receptor.

This result suggests a possible approach to improving the efficacy of treatment for alcohol abuse through the design of better medications than naltrexone, said Fields, who collaborated with Mitchell in the design and analysis of the study.

Fields explained that naltrexone, which prevents binding at opioid receptor sites, is not widely accepted as a treatment for alcohol dependence -- "not because it isn't effective at reducing drinking, but because some people stop taking it because they don't like the way it makes them feel," he said.

"Naltrexone blocks more than one opioid receptor, and we need to know which blocking action reduces drinking and which causes the unwanted side effects," he said. "If we better understand how endorphins control drinking, we will have a better chance of creating more targeted therapies for substance addiction. This paper is a significant step in that direction because it specifically implicates the Mu opioid receptor in alcohol reward in humans."

Co-authors of the study are James P. O'Neill and Mustafa Janabi of Lawrence Berkeley Laboratory and Shawn M. Marks and William J. Jagust, MD, of LBL and the University of California, Berkeley.

The study was supported by funds from the Department of Defense and by State of California Funds for Research on Drug and Alcohol Abuse.

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Printing off the paper: Pushing the boundaries of the burgeoning technology of 3-D printing

Printing off the paper: Pushing the boundaries of the burgeoning technology of 3-D printing

  11:56:00 PM    Science Lover

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Imagine being able to "print" an entire house. Or a four-course dinner. Or a complete mechanical device such as a cuckoo clock, fully assembled and ready to run. Or a printer capable of printing ... yet another printer?

One of the 3-D printers at work in the Mediated Matter
group at the MIT Media Lab. Photo: Melanie Gonick

These are no longer sci-fi flights of fancy. Rather, they are all real (though very early-stage) research projects underway at MIT, and just a few ways the Institute is pushing forward the boundaries of a technology it helped pioneer nearly two decades ago. A flurry of media stories this year have touted three-dimensional printing — or “3DP” — as the vanguard of a revolution in the way goods are produced, one that could potentially usher in a new era of “mass customization.”

One of the first practical 3-D printers, and the first to be called by that name, was patented in 1993 by MIT professors Michael Cima, now the Sumitomo Electric Industries Professor of Engineering, and Emanuel Sachs, now the Fred Fort Flowers (1941) and Daniel Fort Flowers (1941) Professor of Mechanical Engineering. Unlike earlier attempts, this machine has evolved to create objects made of plastic, ceramic and metal. The MIT-inspired 3DPs are now in use “all over the world,” Cima says.

The initial motivation was to produce models for visualization — for architects and others — and help streamline the development of new products, such as medical devices. Cima explains, “The slow step in product development was prototyping. We wanted to be able to rapidly prototype surgical tools, and get them into surgeons’ hands to get feedback.”

3DP technology involves building up a shape gradually, one thin layer at a time. The device uses a “stage” — a metal platform mounted on a piston — that’s raised or lowered by a tiny increment at a time. A layer of powder is spread across this platform, and then a print head similar to those used in inkjet printers deposits a binder liquid onto the powder, binding it together. Then, the platform is lowered infinitesimally, another thin layer of powder is applied on top of the last, and the next layer of binder is deposited.

Made to order

With its layers of powder, such a system can make complex shapes that earlier liquid-based 3DP systems could not produce. And different combinations of powders and binders could make a variety of materials — “anything you can make from powders: ceramics, metals, plastics,” Cima says — or even a mix of different materials in the same printed object, using different liquids in the print heads, like the different colors of ink in an inkjet printer.

In one early version, the powder was aluminum oxide, the binder was colloidal silica, and the resulting solid objects were brittle, similar to materials sometimes used as molds for metal casting. They provided, for the first time, a relatively simple way to get one’s hands on a three-dimensional version of just about any shape that could be sketched by computer-assisted design (CAD) software, before manufacturers committed to mass production at much greater cost.

Over the years, the three MIT researchers and one of the companies that licensed the MIT patent, Z Corp., added new variations, including the ability to include colors in printed objects and to use a variety of materials. The ability to print metal objects, in particular, extended the technology from just a way of visualizing new designs to a means of manufacturing metal molds used for the injection molding of plastic parts.

Samuel Allen SM ’71, PhD ’75, the POSCO Professor of Physical Metallurgy and chair of the MIT faculty, spent a decade developing the metal-printing process. In producing molds for injection molding, he says, “the plastic shapes can be quite complicated, with round surfaces and thin walls.” In addition to the shapes of the finished parts, the molds need to have channels for the plastic material to be injected, and they have to be designed so that the resulting pieces can cool uniformly without warping. The 3DP process made it possible to make “parts you could not make through conventional machining,” Allen says.

Manufacturing companies took a strong interest in this work because it enabled “doing a complete design for a tool in days, rather than months,” he adds. “That means you can afford to go through more design iterations.”

Time for a snack

3DP has since branched out in a wide array of directions, at various companies and research institutions around the world. Applications have included everything from the printing of customized prosthetic limbs to nanoprinting of tiny machinery to a project at the MIT Media Lab developing machines to print food ranging from candies to complete meals. One former Media Lab student, Peter Schmitt PhD ’11, working with Media Lab IP consultant Bob Swartz, has printed entire working clocks — with all their gears, chains, faces and hands in a single unit — ready to start ticking as soon as the surplus powder is washed away.

“Mass production is only a couple of hundred years old,” Swartz says. Now, “we’re moving into an area where things will no longer be mass produced.” With 3DP, a basic pattern can be modified to fit an individual’s size, fit and personal tastes before printing.

These clocks were primarily intended to demonstrate that complex devices could be printed as a unit — but one clock took about 100 hours of printing time to produce. “That’s completely impractical for any kind of mass production,” Swartz says, “but it’s my belief that one can get orders-of-magnitude improvements” in the production speed. “It changes the way we think about production.”



Printing better materials

Another variant underway now is a system being developed by Neri Oxman PhD ’10, the Media Lab’s Sony Corporation Career Development Assistant Professor of Media Arts and Sciences, and her graduate student Steven Keating for “printing” concrete. Their ultimate aim: printing a complete structure, even a whole building.

Why do that, instead of the tried-and-true method of casting concrete in wooden forms that dates from the heyday of the Roman Empire? In part, Oxman explains, because it opens up new possibilities in both form and function. Not only would it be possible to create fanciful, organic-looking shapes that would be difficult or impossible using molds, but the technique could also allow the properties of the concrete itself to vary continuously, producing structures that are both lighter and stronger than conventional concrete.

To illustrate this, Keating uses the example of a palm tree compared to a typical structural column. In a concrete column, the properties of the material are constant, resulting in a very heavy structure. But a palm tree’s trunk varies: denser at the outside and lighter toward the center. As part of his thesis research, he has already made sections of concrete with the same kind of variations of density.

“Nature always uses graded materials,” Keating says. Bone, for example, consists of “a hard, dense outer shell, and an interior of spongy material. It gives you a high strength-to-weight ratio. You don’t see that in man-made materials.” Not yet, at least.

Concrete samples made by hand to illustrate the concept of density gradient in concrete. A team from the MIT Media Lab hopes to be able to print such materials with a 3-D printer.Photo: Steven Keating, Timothy Cooke and John Fernández

Variable-density printing is not just about large-scale objects. For example, Oxman has used a similar system to produce a glove with sections that are stiff and others that are flexible, designed to help prevent the wearer from developing carpal tunnel syndrome. She has also designed a chair made of different polymers, producing stiff areas for structural support and flexible areas for comfort, all printed out as a single unit.

Peter Schmitt, now a visiting scientist at the Media Lab, is pushing the technology in an even more sci-fi direction, trying to “build machines that could build machines,” he says. So far, he’s succeeded in making machines that can make many of the parts for another machine, but there remain many obstacles in establishing connections among these — and it’s still more of an intellectual exercise than a practical system, he concedes. “There are better ways to make the parts,” he says. “But at some point, these kinds of things will happen.” 

This story is republished courtesy of MIT News (http://web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.

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Scientists Have New Help Finding Their Way Around Brain's Nooks and Crannies

Scientists Have New Help Finding Their Way Around Brain's Nooks and Crannies

  12:53:00 AM    Science Lover

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Like explorers mapping a new planet, scientists probing the brain need every type of landmark they can get. Each mountain, river or forest helps scientists find their way through the intricacies of the human brain.

Scientists have found a way to use MRI scanning data 
to map myelin, a white sheath that covers some brain 
cell branches. Such maps, previously only available via 
dissection, help scientists determine precisely where they 
are at in the brain. Red and yellow indicate regions with 
high myelin levels; blue, purple and black areas have low 
myelin levels. (Credit: David Van Essen)

Researchers at Washington University School of Medicine in St. Louis have developed a new technique that provides rapid access to brain landmarks formerly only available at autopsy. Better brain maps will result, speeding efforts to understand how the healthy brain works and potentially aiding in future diagnosis and treatment of brain disorders, the researchers report in the Journal of Neuroscience Aug. 10.

The technique makes it possible for scientists to map myelination, or the degree to which branches of brain cells are covered by a white sheath known as myelin in order to speed up long-distance signaling. It was developed in part through the Human Connectome Project, a $30 million, five-year effort to map the brain's wiring. That project is headed by Washington University in St. Louis and the University of Minnesota.

"The brain is among the most complex structures known, with approximately 90 billion neurons transmitting information across 150 trillion connections," says David Van Essen, PhD, Edison Professor and head of the Department of Anatomy and Neurobiology at Washington University. "New perspectives are very helpful for understanding this complexity, and myelin maps will give us important insights into where certain parts of the brain end and others begin."

Easy access to detailed maps of myelination in humans and animals also will aid efforts to understand how the brain evolved and how it works, according to Van Essen.

Neuroscientists have known for more than a century that myelination levels differ throughout the cerebral cortex, the gray outer layer of the brain where most higher mental functions take place. Until now, though, the only way they could map these differences in detail was to remove the brain after death, slice it and stain it for myelin.

Washington University graduate student Matthew Glasser developed the new technique, which combines data from two types of magnetic resonance imaging (MRI) scans that have been available for years.



"These are standard ways of imaging brain anatomy that scientists and clinicians have used for a long time," Glasser says. "After developing the new technique, we applied it in a detailed analysis of archived brain scans from healthy adults."

As in prior studies, Glasser's results show highest myelination levels in areas involved with early processing of information from the eyes and other sensory organs and control of movement. Many brain cells are packed into these regions, but the connections among the cells are less complex. Scientists suspect that these brain regions rely heavily on what computer scientists call parallel processing: Instead of every cell in the region working together on a single complex problem, multiple separate teams of cells work simultaneously on different parts of the problem.

Areas with less myelin include brain regions linked to speech, reasoning and use of tools. These regions have brain cells that are packed less densely, because individual cells are larger and have more complex connections with neighboring cells.

"It's been widely hypothesized that each chunk of the cerebral cortex is made up of very uniform information-processing machinery," Van Essen says. "But we're now adding to a picture of striking regional differences that are important for understanding how the brain works."

According to Van Essen, the technique will make it possible for the Connectome project to rapidly map myelination in many different research participants. Data on many subjects, acquired through many different analytical techniques including myelination mapping, will help the resulting maps cover the range of anatomic variation present in humans.

"Our colleagues are clamoring to make use of this approach because it's so helpful for figuring out where you are in the cortex, and the data are either already there or can be obtained in less than 10 minutes of MRI scanning," Glasser says.

This research was funded by the National Institutes of Health (NIH).

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New Way to Measure Expansion of Universe

New Way to Measure Expansion of Universe

  12:38:00 AM    Science Lover

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Using a measurement of the clustering of the galaxies surveyed, plus other information derived from observations of the early universe, researchers have measured the Hubble constant with an uncertainly of less than 5 percent. The new work draws on data from a survey of more than 125,000 galaxies.

The 6df Galaxy Survey data, each dot is a galaxy and 
Earth is at the center of the sphere. (Credit: Image courtesy 
of International Centre for Radio Astronomy Research)

A PhD student from The International Centre for Radio Astronomy Research (ICRAR) in Perth has produced one of the most accurate measurements ever made of how fast the Universe is expanding.

Florian Beutler, a PhD candidate with ICRAR at the University of Western Australia, has calculated how fast the Universe is growing by measuring the Hubble constant.

"The Hubble constant is a key number in astronomy because it's used to calculate the size and age of the Universe," said Mr Beutler.

As the Universe swells, it carries other galaxies away from ours. The Hubble constant links how fast galaxies are moving with how far they are from us.

By analysing light coming from a distant galaxy, the speed and direction of that galaxy can be easily measured. Determining the galaxy's distance from Earth is much more difficult. Until now, this has been done by observing the brightness of individual objects within the galaxy and using what we know about the object to calculate how far away the galaxy must be.

This approach to measuring a galaxy's distance from Earth is based on some well-established assumptions but is prone to systematic errors, leading Mr Beutler to tackle the problem using a completely different method.



Published July 26 in the Monthly Notices of the Royal Astronomical Society, Mr Beutler's work draws on data from a survey of more than 125,000 galaxies carried out with the UK Schmidt Telescope in eastern Australia. Called the 6dF Galaxy Survey, this is the biggest survey to date of relatively nearby galaxies, covering almost half the sky.

Galaxies are not spread evenly through space, but are clustered. Using a measurement of the clustering of the galaxies surveyed, plus other information derived from observations of the early Universe, Mr Beutler has measured the Hubble constant with an uncertainly of less than 5%.*

"This way of determining the Hubble constant is as direct and precise as other methods, and provides an independent verification of them," says Professor Matthew Colless, Director of the Australian Astronomical Observatory and one of Mr Beutler's co-authors. "The new measurement agrees well with previous ones, and provides a strong check on previous work."

The measurement can be refined even further by using data from larger galaxy surveys.

"Big surveys, like the one used for this work, generate numerous scientific outcomes for astronomers internationally," says Professor Lister Staveley-Smith, ICRAR's Deputy Director of Science.

* The new measurement of the Hubble constant is 67.0 ± 3.2 km s-1 Mpc-1

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Functioning Small Intestine Created in Laboratory Experiments

Functioning Small Intestine Created in Laboratory Experiments

  9:38:00 AM    Science Lover

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Researchers at The Saban Research Institute of Children's Hospital Los Angeles have successfully created a tissue-engineered small intestine in mice that replicates the intestinal structures of natural intestine -- a necessary first step toward someday applying this regenerative medicine technique to humans.

Tracy C. Grikscheit, MD works at the Saban Research Institute of Children's Hospital Los Angeles. (Credit: Photo courtesy of Children's Hospital Los Angeles)

The study led by Tracy C. Grikscheit, MD -- "A Multicellular Approach Forms a Significant Amount of Tissue-Engineered Small Intestine in the Mouse" -- has been published in the July issue of Tissue Engineering Part A, a biomedical journal.

"In this paper, we are able to report that we can grow tissue-engineered intestine in a mouse model, which opens the doors of basic biology to understand how to grow this tissue better," said Dr. Grikscheit, who is also an assistant professor of surgery at the Keck School of Medicine of the University of Southern California.

As a pediatric surgeon, Dr. Grikscheit is concerned with finding solutions for some of her more vulnerable patients -- newborns. Infants born prematurely are at increased risk for a gastrointestinal disease called necrotizing enterocolitis (NEC), which occurs when the intestine is injured. The cause is unknown.

Early treatment of NEC is essential to stop the potentially life-threatening leakage of bacteria into the abdomen. Often, the only solution is surgical removal of the small intestine. However, this option leaves the baby dependent on intravenous feeding and at risk for liver damage from subsequent intravenous nutrition. Organ transplants are possible but not a long-term solution, with only a 50 percent chance the grafted intestine will last past the child's 5th birthday.

Dr. Grikscheit, a member of The Saban Research Institute's Developmental Biology and Regenerative Medicine program, envisions a better solution. "The small intestine is an exquisitely regenerative organ. The cells are constantly being lost and replaced over the course of our entire lives," she explained. "Why not harness that regenerative capacity to benefit these children?"



Working in the laboratory, the research team took samples of intestinal tissue from mice. This tissue was composed of the layers of the various cells that make up the intestine -- including muscle cells and the cells that line the inside, known as epithelial cells. The investigators then transplanted that mixture of cells within the abdomen on biodegradable polymers or "scaffolding."

What the team wanted to happen did -- new, engineered small intestines grew and had all of the cell types found in native intestine. Because the transplanted cells had carried a green label, the scientists could identify which cells had been provided -- and all of the major components of the tissue-engineered intestine derived from the implanted cells. Critically, the new organs contained the most essential components of the originals.

"What is novel about this research is that this tissue-engineered intestine contains every important cell type needed for functional intestine. For children with intestinal failure, we are always looking for long-term, durable solutions that will not require the administration of toxic drugs to ensure engraftment. This tissue-engineered intestine, which has all of the critical components of the mature intestine, represents a truly exciting albeit preliminary step in the right direction," said Henri Ford, MD, Vice President and Surgeon-in-Chief at Children's Hospital Los Angeles.

"We demonstrated that we are providing all of the important cells -- the muscle, nerve, epithelium, and some of the blood vessels," noted Frédéric Sala, PhD, lead author. "All of these are critical to proper functioning of the tissue, and now we know their origins." Next up are additional tissue-growing experiments -- each one of which may bring that much closer the prospects of clinical testing and a solution for babies in need.

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Flapping micro air vehicles inspired by swifts

Flapping micro air vehicles inspired by swifts

  3:50:00 PM    Science Lover

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Scientists have designed a micro aircraft that will be able to flap, glide and hover like a bird.

This shows the wake of a swift in slow forward flight, the new design mimics these birds to improve MAV performance. Credit: William Thielicke

Researchers from the Biomimetics-Innovation-Centre in Germany have been inspired by birds to produce a new versatile design of Micro air vehicle (MAV) that combines flapping wings, which allow it to fly at slow speeds and hover, with the ability to glide, ensuring good quality images from any on-board camera.

"In birds, the combination of demanding tasks like take-off, travelling long distances, manoeuvring in confined areas and landing is daily practice," explains PhD researcher Mr. William Thielicke, who is presenting this work at the Society for Experimental Biology Annual Conference in Glasgow on the 2nd of July.

Micro air vehicles (MAVs) are small unmanned
aircraft, often used for rescue or reconnaissance
missions in areas where it would be dangerous
or impractical for humans to go. Credit: William
Thielicke

This innovative design was inspired by one bird in particular, the swift. "We know that swifts are very manoeuvrable and they can glide very efficiently. So we thought these birds would be a very good starting point for an energy efficient flapping-wing MAV," says Mr. Thielicke.

While fixed wing MAVs are energy efficient, their manoeuvrability is low. The new design would allow the flapping wing MAV to glide, improving energy efficiency and ensuring good images but when needed it can also slow its flight and manoeuvre in confined spaces.

"Although the models are not yet ready to be used, initial tests are positive and we hope that this design will combine the best of both worlds," says Mr. Thielicke.

Provided by Society for Experimental Biology

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Researchers can predict future actions from human brain activity

Researchers can predict future actions from human brain activity

  2:42:00 AM    Science Lover

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Bringing the real world into the brain scanner, researchers at The University of Western Ontario from The Centre for Brain and Mind can now determine the action a person was planning, mere moments before that action is actually executed.

A volunteer completes tasks while in the functional magnetic
imaging (fMRI) machine. This research project focuses
on understanding how the human brain plans actions.

The findings were published this week in the prestigious Journal of Neuroscience, in the paper, "Decoding Action Intentions from Preparatory Brain Activity in Human Parieto-Frontal Networks."



"This is a considerable step forward in our understanding of how the human brain plans actions," says Jason Gallivan, a Western Neuroscience PhD student, who was the first author on the paper.

University of Western Ontario researchers Jody Culham and Jason Gallivan describe how they can use a fMRI to determine the action a person was planning, mere moments before that action is actually executed. Credit: The University of Western Ontario

Over the course of the one-year study, human subjects had their brain activity scanned using functional magnetic resonance imaging (fMRI) while they performed one of three hand movements: grasping the top of an object, grasping the bottom of the object, or simply reaching out and touching the object. The team found that by using the signals from many brain regions, they could predict, better than chance, which of the actions the volunteer was merely intending to do, seconds later.

"Neuroimaging allows us to look at how action planning unfolds within human brain areas without having to insert electrodes directly into the human brain. This is obviously far less intrusive," explains Western Psychology professor Jody Culham, who was the paper's senior author.

Gallivan says the new findings could also have important clinical implications: "Being able to predict a human's desired movements using brain signals takes us one step closer to using those signals to control prosthetic limbs in movement-impaired patient populations, like those who suffer from spinal cord injuries or locked-in syndrome."

                    Brain timecourse video of subject's fMRI image during experiment

Provided by University of Western Ontario

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Tiny Ring Laser Accurately Detects and Counts Nanoparticles

Tiny Ring Laser Accurately Detects and Counts Nanoparticles

  8:05:00 PM    Science Lover

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A tiny doughnut-shaped laser is the latest marvel of silicon microminiaturization, but instead of manipulating bits it detects very small particles. Small particles play a big -- and largely unnoticed -- role in our everyday lives. Virus particles make us sick, salt particles trigger cloud formation, and soot particles sift deep into our lungs and make it harder to breathe.

Whispering-gallery microlasers can count 
and measure nano-scale synthetic or biological 
particles. As this conceptual illustration shows, 
a particle disturbs the lasing "mode" to split 
into two frequencies (shown here as two different 
colors) and the frequency split acts a ruler that 
allows the particle to be measured. The inset 
at the top right shows a particle landing on the 
microlaser (a torus supported by a pedestal). 
Lina He, a graduate student in electrical and 
systems engineering at Washington University 
in St. Louis, and her co-workers demonstrated 
that the microlasers can detect particles 10 
nanometers in radius. Their resolution limit is 
about one nanometer. (Credit: J. Zhu, L. He, 
S. K. Ozdemir, and L. Yang/WUSTL)

The sensor belongs to a category called whispering gallery resonators, which work like the famous whispering gallery in St. Paul's Cathedral in London, where someone on the one side of the dome can hear a message spoken to the wall by someone on the other side. Unlike the dome, which has resonances or sweet spots in the audible range, the sensor resonates at light frequencies.

Light traveling round the micro-laser is disturbed by a particle that lands on the ring, changing the light's frequency. The ring can count the touch-down of as many as 800 nanoparticles before the signals begin to be lost in the noise. By exciting more than one mode in the ring, scientists can double-check the accuracy of the count. And by changing the "gain medium," they can adapt the sensor for water rather than air.

Lan Yang, PhD, assistant professor of electrical and systems engineering at Washington University in St. Louis who leads the team that fabricated the new sensor, says that there is already lively interest in its commercialization in fields ranging from biology to aerosol science. The sensor is described and characterized in the June 26 online edition of Nature Nanotechnology.

Whispering gallery resonator becomes microlaser

A whispering gallery resonator supports "frequency degenerate modes" (modes, or patterns of excitation in the ring, with the same frequency, one traveling clockwise and the other counterclockwise around the ring.

The mode fields have "evanescent tails" that penetrate the surface of the ring and probe the surrounding medium. When a particle lands on one of the "hot spots" it scatters energy from one of the modes into the other, and the modes adopt slightly different resonance frequencies. This is referred to as mode splitting.

In an earlier work, Yang team used mode splitting in a simple glass ring that functioned as a waveguide for light coupled into it from outside. Because the ring was passive, the external-laser had to be an expensive tunable laser so that it could scan a frequency range looking for the ring's resonances to measure mode splitting. (For more information on this sensor see "Tiny sensor takes measure of nanoparticles.")

The new sensor differs from earlier whispering gallery resonators in that it is itself a miniature laser rather than the resonating cavity of an external laser.

The new sensor is also glass but glass laced with atoms of the rare earth elements that serve as a "gain medium." The glass is doped with rare-earth atoms and when an external light source boosts enough of them into an excited state, the ring begins to lase at its own preferred frequency.

When a particle lands on the microlaser, a single lasing line splits into two slightly different frequencies.

A simple way of measuring the frequency splitting is to mix the split laser modes in a photodetector, which produces a "beat frequency" that corresponds to the frequency difference.

"The tiny sensors are mass produced by sol-gel method on silicon wafer, and it is easy to switch the gain medium" says Lina He, a graduate student and first author of the paper. "The resonators are made by mixing the rare-earth ions of choice into a solution of tetraethoxysilane, water and hydrochloric acid. The solution is heated until it becomes viscous and then spin-coated on a silicon wafer and annealed to remove solvents and complete the transition to amorphous glass. The thin film of glass is then etched to create silica disks supported underneath by silicon pillars. As a final step, the rough silica disks are reflowed into smooth toroids by laser annealing."

Active sensor outperforms passive one



"The light used for sensing is generated inside the resonator itself, and so it is purer than the light in the passive sensor," says Yang "When the light is not that pure, you might not be able to see small frequency changes. But the active sensor hits one frequency -- it has a really narrow linewidth -- and so it is much more sensitive."

The microlaser is orders of magnitude more sensitive than the passive resonator, she says. Its effective resolution limit is about one nanometer. One nanometer is to a meter, what a marble is to Earth.

Moreover, because the laser is now in the ring rather than coupled to it, the entire system is simpler and more self contained. "Now you just need a light source to excite the optical medium," says Yang, "and you can use a cheap laser diode for that instead of an expensive tunable laser."

Detecting many particles

The effect of a particle on a lasing mode depends on the particle's "polarizability," which is a function of its size and refractive index. To cover the possibilities, the Washington University team tested the micro-laser's performance with nanoparticles of various sizes made of various materials, including polystyrene (packing peanuts), virions (virus particles) and gold.

As particles enter the "mode volume" of the micro-laser one by one, the scientists can see a discrete upward or downward jump in the beat frequency. Each discrete jump signals the binding of a particle on the ring, and the number of the jumps reflects the number of particles.

Because the "resonator field" traps the particles on the resonator, once landed, they rarely drop off. But the team found they were able to count many particles before the losses induced by the particles made the laser linewidths so broad they couldn't detect changes in frequency splitting due to the latest arrival.

For example, they were able to detect and count as many as 816 gold nanoparticles using the same laser mode.

"When the line broadening is comparable to the change in splitting, then you're done," says Yang. "However, the whole resonator is fabricated on the chip, so you could just move on to the next resonator if necessary."

Doubling up for accuracy

The micro-laser can support more than one laser mode at a time. "By controlling the overlap of the pump light with the gain medium, you can excite more than one laser line," says Sahin Kaya Ozdemir, PhD, a research associate and co-author. "Then when a particle lands on the ring, each laser line will split into two, and generate a beat frequency. So you will have two beat frequencies instead of one."

That's an advantage, he explains, because the beat frequency depends in part on where the particle lands on the ring. If there is only one laser line and the particle falls between "hot spots" it might not be detected. The second beat frequency prevents these "false negatives," ensuring that every particle produces a detectable beat frequency.

Detecting particles in water

The microlasers intended to sense particles in air had been doped with erbium, a rare-earth element whose optical properties are well matched with those of air. In a final experiment designed to see whether this technique could be used to sense particles in water or blood, the team fabricated sensors that were doped with ytterbium rather than erbium.Ytterbium lases at wavelengths with low absorption of light by water

Yang's team has already begun working to make use of the enhanced sensitivity provided by the microlaser for studying various problems. In terms of applications, "the near-term use will be the monitoring of dynamic behaviors of particles in response to environmental and chemical changes at single particle resolution," says Yang.

The next step, the team see is to engineer the surface of these tiny microlasers to detect DNA and individual biological molecules. If the DNA is tagged with engineered nanoparticles, the micro-laser sensor can count individual DNA molecules or fragments of molecules.

Listening to Yang it is hard to escape the impression that you're hearing for the first time about an astonishing device that will one day be as ubiquitous -- and probably as underappreciated -- as the logic gates in our microwaves, cellphones and cars.

The Washington University in St. Louis team behind these results includes: L. He, W. Kim and J. Zhu, graduate students; S. K. Ozdemir, PhD, a research associate, and L. Yang, PhD, assistant professor in electrical and systems engineering.

This work is supported by National Science Foundation.

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Cutting Edge Training Developed the Human Brain 80,000 Years Ago

Cutting Edge Training Developed the Human Brain 80,000 Years Ago

  6:26:00 PM    Science Lover

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Advanced crafting of stone spearheads contributed to the development of new ways of human thinking and behaving, according to new findings by archaeologists from Lund University. The technology took a long time to acquire, required step by step planning and increased social interaction across the generations. This led to the human brain developing new abilities.

Cave in South Africa where excavations have taken 
place. (Credit: Image courtesy of Lund University)

Some 200,000 years ago, small groups of people wandered across Africa, looking anatomically much like present-day humans, but not thinking the way we do today. Studies of fossils and the rate of mutations in DNA show that the human species to which we all belong -- Homo sapiens sapiens -- has existed for 200,000 years.

But the archaeological research of recent years has shown that, even though the most ancient traces of modern humans are 200,000 years old, the development of modern cognitive behaviour is probably much younger. For about 100,000 years, there were people who looked like us, but who were cognitively and socially very different from us.



It is precisely that period of transformation that the researchers at Lund University in Sweden have studied. In the next issue of the Journal of Human Evolution, they present new findings on the early modern humans that existed in what is now South Africa, approximately 80,000 years ago.

The findings show that people at that time used advanced technology for the production of spearheads and that the complicated crafting process likely developed the working memory and social life of humans.

"When the technology was passed from one generation to the next, from adults to children, it became part of a cultural learning process which created a socially more advanced society than before. This affected the development of the human brain and cognitive ability," says Anders Högberg, PhD.

The technology led to increased social interaction within and across the generations. This happened because the crafting of stone spearheads took a long time to learn and required a lot of knowledge, both theoretical and practical. Producing a stone spearhead also required the ability to plan in several stages. This social learning contributed to the subsequent development of early modern humans' cognitive ability to express symbolism and abstract thoughts through their material culture, for example in the form of decorated objects.

"The excavations have been carried out in a small cave; the location we have studied is called Hollow Rock Shelter and lies 250 km north of Cape Town. We are cooperating with the University of Cape Town and the research we have just published is part of a larger research project on this location," says Professor Lars Larsson.

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Non-coding RNA has role in inherited neurological disorder -- and maybe other brain diseases too

Non-coding RNA has role in inherited neurological disorder -- and maybe other brain diseases too

  1:26:00 AM    Science Lover

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A team of scientists, led by researchers at the University of California, San Diego School of Medicine, have uncovered a novel mechanism regulating gene expression and transcription linked to Spinocerebellar ataxia 7, an inherited neurological disorder. The discovery promises to have broad ramifications, suggesting that abundant non-coding transcripts of ribonucleic acid (RNA) may be key players in neurological development and function, and could be powerful targets for future clinical therapies.

Researchers have discovered that expression
of the ataxin‑7 gene - the cause of the
neurological disorder spinocerebellar
ataxia type 7 - has two regulators: a highly
conserved, multi‑tasking protein called
CTCF and, surprisingly, an adjacent promoter
containing non‑coding RNA.
Credit: Illustration courtesy of Christina
Takamatsu‑Butler, UC San Diego.

The research, headed by Albert La Spada, MD, PhD, chief of the division of genetics in the UCSD department of pediatrics, and professor of cellular and molecular medicine, neurosciences and biological sciences, is published in the June 22 issue of the journal Neuron.

"Our paper highlights a number of important emerging themes in our understanding of gene regulation in the brain," said La Spada, who is also associate director of the UCSD Institute for Genomic Medicine.

"With the advent of new technologies, science has learned that the vast majority of our transcripts are non-coding," said La Spada. "The challenge going forward is to determine what they do do, and if they have specific functions. It now seems increasingly likely that a multitude of these non-coding RNAs help finely tune transcription regulation in the brain, and perturbation of their work is linked to disease. If we can figure out exactly how, we should be able to gain new insights into how the brain is so precisely regulated – knowledge that may help us better understand how the brain works."



Spinocerebellar ataxia 7 is one of several types of spinocerebellar ataxia (SCA), genetic degenerative disorders characterized by atrophy in the cerebellum of the brain, progressive loss of physical coordination – and in the case of type 7 – retinal degeneration that can result in blindness. There is currently no known cure.

Many SCAs are classified as polyglutamine diseases, caused when a protein associated with the disease contains too many repeats of the amino acid glutamine. Polyglutamine diseases are also known as "CAG Triplet Repeat Disorders" because CAG is the sequence of nucleic acids that codes for glutamine.

La Spada and colleagues have long studied SCA. In 2001, they were the first to demonstrate that SCA7 retinal degeneration was the result of transcription dysregulation of ataxin-7, the protein associated with SCA7. Following up, they decided to learn how the gene that expresses ataxin-7 is itself regulated.

The researchers found not one, but two, regulators. The first is called CTCF, a highly conserved protein that regulates a variety of transcriptional processes, most notable establishing insulator domains and controlling genomic imprinting. But they also discovered an adjacent, alternative promoter dubbed intron 2 promoter (P2A) and a transcribed antisense, non-coding RNA, which they labeled SpinoCerebellarAtaxia-AntisenseNoncodingTranscript1 or SCAANT1.

Antisense RNA is single-stranded ribonucleic acid whose primary function appears to be as an inhibitor or suppressor of a gene, though sometimes it can promote gene expression instead. Most antisense RNAs are non-coding, meaning that their sequences do not provide information for making proteins. Even though non-coding RNAs do not provide instructions for the production of vital proteins, they comprise the bulk of the human genome. A major challenge for biomedical research in the 21st century is to figure what they do, and how they do it.

In their Neuron paper, La Spada and colleagues highlight one function, at least for SCAANT1. When they investigated how CTCF regulated ataxin-7 gene expression in transgenic mice, they discovered that CTCF promotes the production of SCAANT1 which in turn represses the newly discovered ataxin-7 sense promoter P2A. In mice lacking SCAANT1, sense promoter P2A is de-repressed, allowing a mutant ataxin-7 gene to be expressed, resulting in mice with a version of SCA7. The scientists found a similar lack of antisense SCAANT1 in the fibroblasts and white blood cells taken from human patients with SCA7, implicating deregulation of this pathway in the disease process.

As many inherited neurological disorders are now known to exhibit such overlapping "bidirectional" transcription, the findings in SCA7 could shed light on similar abnormalities with non-coding RNA function in a number of brain diseases.

Provided by University of California - San Diego

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Implant to Translate Thoughts Into Movement

Implant to Translate Thoughts Into Movement

  2:04:00 PM    Science Lover

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A brain implant developed at the University of Michigan uses the body's skin like a conductor to wirelessly transmit the brain's neural signals to control a computer, and may eventually be used to reactivate paralyzed limbs.

A brain implant developed at the University of Michigan uses the body's skin like a conductor to wirelessly transmit the brain's neural signals to control a computer, and may eventually be used to reactivate paralyzed limbs. (Credit: Photo provided by Euisik Yoon of University of Michigan)

The implant is called the BioBolt, and unlike other neural interface technologies that establish a connection from the brain to an external device such as a computer, it's minimally invasive and low power, said principal investigator Euisik Yoon, a professor in the U-M College of Engineering, Department of Electrical Engineering and Computer Science.

Currently, the skull must remain open while neural implants are in the head, which makes using them in a patient's daily life unrealistic, said Kensall Wise, the William Gould Dow Distinguished University professor emeritus in engineering.

BioBolt does not penetrate the cortex and is completely covered by the skin to greatly reduce risk of infection. Researchers believe it's a critical step toward the Holy Grail of brain-computer interfacing: allowing a paralyzed person to "think" a movement.

"The ultimate goal is to be able to reactivate paralyzed limbs," by picking the neural signals from the brain cortex and transmitting those signals directly to muscles, said Wise, who is also founding director of the NSF Engineering Research Center for Wireless Integrated MicroSystems (WIMS ERC). That technology is years away, the researchers say.



Another promising application for the BioBolt is controlling epilepsy, and diagnosing certain diseases like Parkinson's.

The concept of BioBolt is filed for patent and was presented on June 16 at the 2011 Symposium on VLSI Circuits in Kyoto, Japan. Sun-Il Chang, a PhD student in Yoon's research group, is lead author on the presentation.

The BioBolt looks like a bolt and is about the circumference of a dime, with a thumbnail-sized film of microcircuits attached to the bottom. The BioBolt is implanted in the skull beneath the skin and the film of microcircuits sits on the brain. The microcircuits act as microphones to 'listen' to the overall pattern of firing neurons and associate them with a specific command from the brain. Those signals are amplified and filtered, then converted to digital signals and transmitted through the skin to a computer, Yoon said.

Another hurdle to brain interfaces is the high power requirement for transmitting data wirelessly from the brain to an outside source. BioBolt keeps the power consumption low by using the skin as a conductor or a signal pathway, which is analogous to downloading a video into your computer simply by touching the video.

Eventually, the hope is that the signals can be transmitted through the skin to something on the body, such as a watch or a pair of earrings, to collect the signals, said Yoon, eliminating the need for an off-site computer to process the signals.

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Lights and Flat-Panel Displays: Researchers 'Brighten' the Future of Organic Light-Emitting Diode Technology

Lights and Flat-Panel Displays: Researchers 'Brighten' the Future of Organic Light-Emitting Diode Technology

  10:44:00 AM    Science Lover

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Chlorine is an abundant and readily available halogen gas commonly associated with the sanitation of swimming pools and drinking water. Could a one-atom thick sheet of this element revolutionize the next generation of flat-panel displays and lighting technology?

L to R: Z. Wang (PhD Candidate), Professor Zheng-Hong 
Lu, M. Helander (PhD Candidate + Vanier Canada 
Graduate Scholar) holding Cl-ITO enabled OLED 
devices. (Credit: Image courtesy of University of Toronto 
Faculty of Applied Science and Engineering)

In the case of Organic Light-Emitting Diode (OLED) devices, it most certainly can. Primary researchers Michael G. Helander (PhD Candidate and Vanier Canada Graduate Scholar), Zhibin Wang (PhD Candidate), and led by Professor Zheng-Hong Lu of the Department of Materials Science & Engineering at the University of Toronto, have found a simple method of using chlorine to drastically reduce traditional OLED device complexity and dramatically improve its efficiency all at the same time. By engineering a one-atom thick sheet of chlorine onto the surface of an existing industry-standard electrode material (indium tin oxide, ITO) found in today's flat-panel displays, these researchers have created a medium that allows for efficient electrical transport while eliminating the need for several costly layers found in traditional OLED devices.

"It turns out that it's remarkably easy to engineer this one-atom thick layer of chlorine onto the surface of ITO," says Helander. "We developed a UV light assisted process to achieve chlorination, which negates the need for chlorine gas, making the entire procedure safe and reliable."

The team tested their green-emitting "Cl-OLED" against a conventional OLED and found that the efficiency was more than doubled at very high brightness. "OLEDs are known for their high-efficiency," says Helander. "However, the challenge in conventional OLEDs is that as you increase the brightness, the efficiency drops off rapidly."

Using their chlorinated ITO, this team of advanced materials researchers found that they were able to prevent this drop off and achieve a record efficiency of 50% at 10,000 cd/m2 (a standard florescent light has a brightness of approximately 8,000 cd/m2), which is at least two times more efficient than the conventional OLED.

"Our Cl-ITO eliminates the need for several stacked layers found in traditional OLEDs, reducing the number of manufacturing steps and equipment, which ultimately cuts down on the costs associated with setting up a production line," says Professor Zheng-Hong Lu.

"This effectively lowers barriers for mass production and thereby accelerates the adoption of OLED devices into mainstream flat-panel displays and other lighting technologies."

The results of this work are published online in the journal Science on April 14, 2011.

Story Source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Toronto Faculty of Applied Science and Engineering.

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Robot Arm Improves Performance of Brain-Controlled Device

Robot Arm Improves Performance of Brain-Controlled Device

  10:34:00 AM    Science Lover

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The performance of a brain-machine interface designed to help paralyzed subjects move objects with their thoughts is improved with the addition of a robotic arm providing sensory feedback, a new study from the University of Chicago finds.

During the experiment, monkeys used their brain signals to move a computer cursor (red circle) to randomly placed targets (squares). When visual and proprioceptive feedback were included, the monkey's hand was moved by a robotic exoskeleton. The additional sensory information resulted in the cursor hitting the target faster and more directly. (Credit: Courtesy, with permission: Hatsopoulos, et al. The Journal of Neuroscience 2010.)

Devices that translate brain activity into the movement of a computer cursor or an external robotic arm have already proven successful in humans. But in these early systems, vision was the only tool a subject could use to help control the motion.

Adding a robot arm that provided kinesthetic information about movement and position in space improved the performance of monkeys using a brain-machine interface in a study published December 14 in The Journal of Neuroscience. Incorporating this sense may improve the design of "wearable robots" to help patients with spinal cord injuries, researchers said.

"A lot of patients that are motor-disabled might have partial sensory feedback," said Nicholas Hatsopoulos, PhD, Associate Professor and Chair of Computational Neuroscience at the University of Chicago. "That got us thinking that maybe we could use this natural form of feedback with wearable robots to provide that kind of feedback."

In the experiments, monkeys controlled a cursor without actively moving their arm via a device that translated activity in the primary motor cortex of their brain into cursor motion. While wearing a sleeve-like robotic exoskeleton that moved their arm in tandem with the cursor, the monkey's control of the cursor improved, hitting targets faster and via straighter paths than without the exoskeleton.

"We saw a 40 percent improvement in cursor control when the robotic exoskeleton passively moved the monkeys' arm," Hatsopoulos said. "This could be quite significant for daily activities being performed by a paralyzed patient that was equipped with such a system."

When a person moves their arm or hand, they use sensory feedback called proprioception to control that motion. For example, if one reaches out to grab a coffee mug, sensory neurons in the arm and hand send information back to the brain about where one's limbs are positioned and moving. Proprioception tells a person where their arm is positioned, even if their eyes are closed.

But in patients with conditions where sensory neurons die out, executing basic motor tasks such as buttoning a shirt or even walking becomes exceptionally difficult. Paraplegic subjects in the early clinical trials of brain-machine interfaces faced similar difficulty in attempting to move a computer cursor or robot arm using only visual cues. Those troubles helped researchers realize the importance of proprioception feedback, Hatsopoulos said.

"In the early days when we were doing this, we didn't even consider sensory feedback as an important component of the system," Hatsopoulos said. "We really thought it was just one-way: signals were coming from the brain, and then out to control the limb. It's only more recently that the community has really realized that there is this loop with feedback coming back."

Reflecting this loop, the researchers on the new study also observed changes in the brain activity recorded from the monkeys when sensory feedback was added to the set-up. With proprioception feedback, the information in the cell firing patterns of the primary motor cortex contained more information than in trials with only visual feedback, Hatsopoulos said, reflecting an improved signal-to-noise ratio.

The improvement seen from adding proprioception feedback may inform the next generation of brain-machine interface devices, Hatsopoulos said. Already, scientists are developing different types of "wearable robots" to augment a person's natural abilities. Combining a decoder of cortical activity with a robotic exoskeleton for the arm or hand can serve a dual purpose: allowing a paralyzed subject to move the limb, while also providing sensory feedback.

To benefit from this solution, a paralyzed patient must have retained some residual sensory information from the limbs despite the loss of motor function -- a common occurrence, Hatsopoulos said, particularly in patients with ALS, locked-in syndrome, or incomplete spinal cord injury. For patients without both motor and sensory function, direct stimulation of sensory cortex may be able to simulate the sensation of limb movement. Further research in that direction is currently underway, Hatsopoulos said.

"I think all the components are there; there's nothing here that's holding us back conceptually," Hatsopoulos said. "I think using these wearable robots and controlling them with the brain is, in my opinion, probably the most promising approach to take in helping paralyzed individuals regain the ability to move."

Funding for the research was provided by the National Institute of Neurological Disorders and Stroke and the Paralyzed Veterans of America Research Foundation.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect to us.

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