Nano-Spider Molecules Behave Like Robots

Nano-Spider Molecules Behave Like Robots

  1:38:00 AM    Science Lover

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A team of scientists from Columbia University, Arizona State University, the University of Michigan, and the California Institute of Technology (Caltech) have programmed an autonomous molecular "robot" made out of DNA to start, move, turn, and stop while following a DNA track.

The latest installment in DNA nanotechnology has arrived: 
A molecular nanorobot dubbed a "spider" and labeled with 
green dyes traverses a substrate track built upon a DNA 
origami scaffold. It journeys towards its red-labeled goal 
by cleaving the visited substrates, thus exhibiting the 
characteristics of an autonomously moving, behavior-based 
robot at the molecular scale. (Credit: Courtesy of Paul Michelotti)

The development could ultimately lead to molecular systems that might one day be used for medical therapeutic devices and molecular-scale reconfigurable robots -- robots made of many simple units that can reposition or even rebuild themselves to accomplish different tasks.

A paper describing the work appears in the current issue of the journal Nature.

The traditional view of a robot is that it is "a machine that senses its environment, makes a decision, and then does something -- it acts," says Erik Winfree, associate professor of computer science, computation and neural systems, and bioengineering at Caltech.

Milan N. Stojanovic, a faculty member in the Division of Experimental Therapeutics at Columbia University, led the project and teamed up with Winfree and Hao Yan, professor of chemistry and biochemistry at Arizona State University and an expert in DNA nanotechnology, and with Nils G. Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan in Ann Arbor, for what became a modern-day self-assembly of like-minded scientists with the complementary areas of expertise needed to tackle a tough problem.

Shrinking robots down to the molecular scale would provide, for molecular processes, the same kinds of benefits that classical robotics and automation provide at the macroscopic scale. Molecular robots, in theory, could be programmed to sense their environment (say, the presence of disease markers on a cell), make a decision (that the cell is cancerous and needs to be neutralized), and act on that decision (deliver a cargo of cancer-killing drugs).

Or, like the robots in a modern-day factory, they could be programmed to assemble complex molecular products. The power of robotics lies in the fact that once programmed, the robots can carry out their tasks autonomously, without further human intervention.

With that promise, however, comes a practical problem: how do you program a molecule to perform complex behaviors?

"In normal robotics, the robot itself contains the knowledge about the commands, but with individual molecules, you can't store that amount of information, so the idea instead is to store information on the commands on the outside," says Walter. And you do that, says Stojanovic, "by imbuing the molecule's environment with informational cues."

"We were able to create such a programmed or 'prescribed' environment using DNA origami," explains Yan. DNA origami, an invention by Caltech Senior Research Associate Paul W. K. Rothemund, is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns (such as smiley faces or maps of the Western Hemisphere or even electrical diagrams). Exploiting the sequence-recognition properties of DNA base pairing, DNA origami are created from a long single strand of DNA and a mixture of different short synthetic DNA strands that bind to and "staple" the long DNA into the desired shape. The origami used in the Nature study was a rectangle that was 2 nanometers (nm) thick and roughly 100 nm on each side.

The researchers constructed a trail of molecular "bread crumbs" on the DNA origami track by stringing additional single-stranded DNA molecules, or oligonucleotides, off the ends of the staples. These represent the cues that tell the molecular robots what to do -- start, walk, turn left, turn right, or stop, for example -- akin to the commands given to traditional robots.

The molecular robot the researchers chose to use -- dubbed a "spider" -- was invented by Stojanovic several years ago, at which time it was shown to be capable of extended, but undirected, random walks on two-dimensional surfaces, eating through a field of bread crumbs.

To build the 4-nm-diameter molecular robot, the researchers started with a common protein called streptavidin, which has four symmetrically placed binding pockets for a chemical moiety called biotin. Each robot leg is a short biotin-labeled strand of DNA, "so this way we can bind up to four legs to the body of our robot," Walter says. "It's a four-legged spider," quips Stojanovic. Three of the legs are made of enzymatic DNA, which is DNA that binds to and cuts a particular sequence of DNA. The spider also is outfitted with a "start strand" -- the fourth leg -- that tethers the spider to the start site (one particular oligonucleotide on the DNA origami track). "After the robot is released from its start site by a trigger strand, it follows the track by binding to and then cutting the DNA strands extending off of the staple strands on the molecular track," Stojanovic explains.

"Once it cleaves," adds Yan, "the product will dissociate, and the leg will start searching for the next substrate." In this way, the spider is guided down the path laid out by the researchers. Finally, explains Yan, "the robot stops when it encounters a patch of DNA that it can bind to but that it cannot cut," which acts as a sort of flypaper.

Although other DNA walkers have been developed before, they've never ventured farther than about three steps. "This one," says Yan, "can walk up to about 100 nanometers. That's roughly 50 steps."

"This in itself wasn't a surprise," adds Winfree, "since Milan's original work suggested that spiders can take hundreds if not thousands of processive steps. What's exciting here is that not only can we directly confirm the spiders' multistep movement, but we can direct the spiders to follow a specific path, and they do it all by themselves -- autonomously."

In fact, using atomic force microscopy and single-molecule fluorescence microscopy, the researchers were able to watch directly spiders crawling over the origami, showing that they were able to guide their molecular robots to follow four different paths.

"Monitoring this at a single molecule level is very challenging," says Walter. "This is why we have an interdisciplinary, multi-institute operation. We have people constructing the spider, characterizing the basic spider. We have the capability to assemble the track, and analyze the system with single-molecule imaging. That's the technical challenge." The scientific challenges for the future, Yan says, "are how to make the spider walk faster and how to make it more programmable, so it can follow many commands on the track and make more decisions, implementing logical behavior."

"In the current system," says Stojanovic, "interactions are restricted to the walker and the environment. Our next step is to add a second walker, so the walkers can communicate with each other directly and via the environment. The spiders will work together to accomplish a goal." Adds Winfree, "The key is how to learn to program higher-level behaviors through lower-level interactions."

Such collaboration ultimately could be the basis for developing molecular-scale reconfigurable robots -- complicated machines that are made of many simple units that can reorganize themselves into any shape -- to accomplish different tasks, or fix themselves if they break. For example, it may be possible to use the robots for medical applications. "The idea is to have molecular robots build a structure or repair damaged tissues," says Stojanovic.

"You could imagine the spider carrying a drug and bonding to a two-dimensional surface like a cell membrane, finding the receptors and, depending on the local environment," adds Yan, "triggering the activation of this drug."

Such applications, while intriguing, are decades or more away. "This may be 100 years in the future," Stojanovic says. "We're so far from that right now."

"But," Walter adds, "just as researchers self-assemble today to solve a tough problem, molecular nanorobots may do so in the future."

The other coauthors on the paper, "Molecular robots guided by prescriptive landscapes," are Kyle Lund and Jeanette Nangreave from Arizona State University; Anthony J. Manzo, Alexander Johnson-Buck, and Nicole Michelotti from the University of Michigan; Nadine Dabby from Caltech; and Steven Taylor and Renjun Pei from Columbia University. The work was supported by the National Science Foundation, the Army Research Office, the Office of Naval Research, the National Institutes of Health, the Department of Energy, the Searle Foundation, the Lymphoma and Leukemia Society, the Juvenile Diabetes Research Foundation, and a Sloan Research Fellowship.

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Brain's Master Switch Is Verified

Brain's Master Switch Is Verified

  9:20:00 PM    Science Lover

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The protein that has long been suspected by scientists of being the master switch allowing brains to function has now been verified by an Iowa State University researcher.

Yeon-Kyun Shin, professor of biochemistry, 
biophysics and molecular biology at ISU, has 
shown that the protein called synaptotagmin1 
(Syt1) is the sole trigger for the release of 
neurotransmitters in the brain using this 
instrument that allows a new technique called 
single vesicle fusion method. 
(Credit: ISU photo by Bob Elbert)

Yeon-Kyun Shin, professor of biochemistry, biophysics and molecular biology at ISU, has shown that the protein called synaptotagmin1 (Syt1) is the sole trigger for the release of neurotransmitters in the brain.

Prior to this research, Syt1 was thought to be a part of the protein structure (not the sole protein) that triggered the release of neurotransmitters at 10 parts per million of calcium.

Shin's research is published in the current issue of the journal Science.

"Syt1 was a suspect previously, but people were not able to pinpoint that it's the real one, even though there were lots and lots of different trials," said Shin.

"In this case, we are trying to show in the laboratory that it's the real one. So we excluded everything else, and included SNARE proteins -- that's the machinery of the release, and the Syt1 is a calcium-sensing timer."

Syt1 senses, at 10 ppm of calcium, and tells the SNARE complex to open the pore to allow the movement of the neurotransmitters.

Brain activity occurs when neurotransmitters move into a fusion pore.

"We are showing that this Syt1 senses the calcium at 10 ppm, and sends the signal to the SNARE complex to open the fusion pore. That is the process that we are showing right now," Shin said.

Shin and his researchers were able to pinpoint the protein using a new technique called single vesicle fusion method. Using this method, they were able to create and monitor a single fusion event.

Previous research didn't allow scientists to look at single events, and instead required detecting many events and then taking an average of those events, Shin says.

Shin, who has been looking at this brain activity for 15 years, is happy about the discovery.

"We are quite excited that for the first time we are showing that Syt1 is really what triggers the signal in the brain," he said. "This is a really important thing in terms of neurosciences. This is the heart of the molecular part of the brain function."

Shin believes his discovery may be useful in understanding brain malfunctions such as autism, epilepsy and others.

While researching brain function, Shin has previously shown that taking statin drugs to lower cholesterol may actually inhibit some brain function.

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New Nerve Cells -- Even in Old Age: Researchers Find Different Types of Stem Cells in the Brains of Mature and Old Mice

New Nerve Cells -- Even in Old Age: Researchers Find Different Types of Stem Cells in the Brains of Mature and Old Mice

  10:25:00 AM    Science Lover

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After birth the brain loses many nerve cells and this continues throughout life -- most neurons are formed before birth, after which many excess neurons degenerate. However, there are some cells that are still capable of division in old age -- in the brains of mice, at least. According to scientists from the Max Planck Institute of Immunobiology in Freiburg, different types of neuronal stem cells exist that can create new neurons. While they divide continuously and create new neurons in young animals, a large proportion of the cells in older animals persist in a state of dormancy. However, the production of new cells can be reactivated, for example, through physical activity or epileptic seizures. What happens in mice could also be applicable to humans as neurons that are capable of dividing also occur in the human brain into adulthood.

Different types of stem cells in the brain of mature mice. 
(Credit: Verdon Taylor (from: Lugert et al., 
Cell Stem Cell, May 7th, 2010))

The research is published in the journal Cell Stem Cell.

You can't teach an old dog new tricks. The corresponding view that the brain loses learning and memory capacity with advancing age prevailed for a long time. However, neuronal stem cells exist in the hippocampus -- a region of the brain that plays a central role in learning and memory functions -- that can produce new nerve cells throughout life. It is known from tests on mice that the newly formed cells are integrated into the existing networks and play an important role in the learning capacity of animals. Nonetheless, the formation of new cells declines with age and the reasons for this were unknown up to now.

Together with colleagues from Dresden and Munich, the Freiburg researchers have now succeeded in explaining for the first time why fewer new neurons are formed in the adult mouse brain. They managed to identify different populations of neuronal stem cells, thereby demonstrating that the hippocampus has active and dormant or inactive neuronal stem cells. "In young mice, the stem cells divide four times more frequently than in older animals. However, the number of cells in older animals is only slightly lower. Therefore, neuronal stem cells do not disappear with age but are kept in reserve," explains Verdon Taylor from the Max Planck Institute of Immunobiology.

The precise factors that influence the reactivation of dormant stem cells are not yet clear. The cells can, however, be stimulated to divide again. The scientists observed more newborn hippocampal neurons in physically active mice than in their inactive counterparts. "Consequently, running promotes the formation of new neurons," says Verdon Taylor. Pathological brain activity, for example that which occurs during epileptic seizures, also triggers the division of the neuronal stem cells.

Horizontal and radial stem cells

The different stem cell populations are easy to distinguish under the microscope. The first group comprises cells which lie perpendicular to the surface of the hippocampus. Most of these radial stem cells are dormant. As opposed to this, over 80% of the cells in the group of horizontal stem cells -- cells whose orientation runs parallel to the hippocampus surface -- continuously form new cells; the remaining 20% are dormant but sporadically become activated. The activity of genes such as Notch, RBP-J and Sox2 is common to all of the cells.

Radial and horizontal stem cells differ not only in their arrangement, apparently they also react to different stimuli. When the animals are physically active, some radial stem cells abandon their dormant state and begin to divide, while this has little influence on the horizontal stem cells. The result is that more radial stem cells divide in active mice. The horizontal stem cells, in contrast, are also influenced by epileptic seizures.

It would appear that neuronal stem cells are not only found in the brains of mice. The presence of neurons that are formed over the course of life has also been demonstrated in the human hippocamus. Therefore, scientists suspect that different types of active and inactive stem cells also arise in the human brain. It is possible that inactive stem cells in humans can also be activated in a similar way to inactive stem cells in mice. "There are indicators that the excessive formation of new neurons plays a role in epilepsy. The use of neuronal brain stem cells in the treatment of brain injuries or degenerative diseases like Alzheimers may also be possible one day," hopes Verdon Taylor.

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Climate Change and Mountain Building Led to Mammal Diversity Patterns

Climate Change and Mountain Building Led to Mammal Diversity Patterns

  1:22:00 AM    Science Lover

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Travel from the tropics to the poles, and you'll notice that the diversity of mammals declines with distance from the equator. Move from lowland to mountains, and you'll see diversity increase as the landscape becomes more varied. Ecologists have proposed various explanations for these well-known "biodiversity gradients," invoking ecological, evolutionary and historical processes.

Golden-mantled ground squirrel in Utah mountains and fossil squirrel jaw document high rodent diversity in topographically complex western North America today and 16 Million years ago. (Credit: Squirrel photo by Catherine Badgley; Fossil rodent jaw photo by University of California Museum of Paleontology (photo used with permission); Topographic pattern from MyTopo (used with permission))

New findings by University of Michigan researchers John A. Finarelli and Catherine Badgley suggest that the elevational patterns of diversity we see today have appeared, disappeared and reappeared over Earth's history and that these patterns arise from interactions between climate change and mountain building.

The results, published online in the journal Proceedings of the Royal Society B, also have implications for conservation efforts in the face of modern-day global warming, said Finarelli, a visiting assistant professor in the Department of Geological Sciences.

In their study, focused on the Miocene Epoch, which began around 23 million years ago and ended about 5 million years ago, Finarelli and Badgley evaluated diversity for more than 400 rodent species from adjacent regions that differed in geologic history and topography. The geologically "active region," which extends from the Front Range of the Rocky Mountains to the Pacific coast, has experienced several episodes of mountain-building and volcanic activity, and as a result has a topographically complex landscape. In contrast, the relatively flat Great Plains, has been more stable geologically.

The prevailing notion has been that diversity is greater in mountainous regions than in lowlands simply because the topography is more complex. As mountains rise up, new habitats are created, and areas that once were continuous become fragmented. Such changes offer opportunities for new species to arise, increasing diversity.

But climate also enters in, the new study shows. During the Miocene, long-term, global cooling was interrupted by warm intervals. In the active region, diversity increased during a warm interval from 17 to 14 million years ago that coincided with intensified mountain building and volcanic activity, the analysis revealed. During subsequent cooling, diversity declined in the mountains and increased on the plains.

"This pattern suggests that the elevational diversity gradient arises during historical episodes associated with global warming and mountain building," said Badgley, an assistant professor in the Department of Ecology and Evolutionary Biology and a research scientist in the Museum of Paleontology and the Department of Geological Sciences. "This gradient is not a long-term feature of North American biodiversity."

Although the research focused on ancient ecosystems, the findings have implications for modern times, Finarelli said. "Based on our finding that more complex regions are more sensitive to climate change, threatened areas in mountainous regions should be a particular conservation concern, with respect to human-mediated climate change."

The work also highlights the importance of studies that merge the disciplines of paleontology and biogeography, Finarelli said. "By marrying the two subjects, we can gain a better insight into the ecological and evolutionary processes shaping the world around us."

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Peptides May Hold 'Missing Link' to Life

Peptides May Hold 'Missing Link' to Life

  1:47:00 AM    Science Lover

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Emory scientists have discovered that simple peptides can organize into bi-layer membranes. The finding suggests a "missing link" between the pre-biotic Earth's chemical inventory and the organizational scaffolding essential to life.

Researchers tagged one end of peptide chains with an 
NMR label, and then allowed them to assemble to see 
if the ends would interact. The result was a bi-layer 
membrane with inner and outer faces and an additional, 
buried layer that localized functionality within the interior. 
(Credit: Image courtesy of Emory University)

"We've shown that peptides can form the kind of membranes needed to create long-range order," says chemistry graduate student Seth Childers, lead author of the paper recently published by the German Chemical Society's Angewandte Chemie. "What's also interesting is that these peptide membranes may have the potential to function in a complex way, like a protein."

Chemistry graduate student Yan Liang captured images of the peptides as they aggregated into molten globular structures, and self-assembled into bi-layer membranes. The results of that experiment were recently published by the Journal of the American Chemical Society.

"In order to form nuclei, which become the templates for growth, the peptides first repel water," says Liang, who is now an Emory post-doctoral fellow in neuroscience. "Once the peptides form the template, we can now see how they assemble from the outer edges."

In addition to providing clues to the origins of life, the findings may shed light on protein assemblies related to Alzheimer's disease, Type 2 diabetes, and dozens of other serious ailments.

"This is a boon to our understanding of large, structural assemblies of molecules," says Chemistry Chair David Lynn, who helped lead the effort behind both papers, which were collaborations of the departments of chemistry, biology and physics. "We've proved that peptides can organize as bi-layers, and we've generated the first, real-time imaging of the self-assembly process. We can actually watch in real-time as these nano-machines make themselves."

The ability to organize things within compartments and along surfaces underpins all of biology. From the bi-layer phospholipids of cell membranes to information-rich DNA helices, self-assembling arrays define the architecture of life.

But while phospholipids and DNA are complicated molecules, peptides are composed of the simple amino acids that make up proteins. The Miller-Urey experiment demonstrated in 1953 that amino acids were likely to be present on the pre-biotic Earth, opening the question of whether simple peptides could achieve supra-molecular order.

To test how the hollow, tubular structure of peptides is organized, the researchers used specialized solid-state nuclear magnetic resonance (NMR) methods that have been developed at Emory during the past decade. Working with Anil Mehta, a chemistry post-doctoral fellow, Childers tagged one end of peptide chains with an NMR label, and then allowed them to assemble to see if the ends would interact. The result was a bi-layer membrane with inner and outer faces and an additional, buried layer that localized functionality within the interior.

"The peptide membranes combine the long-range structure of cell membranes with the local order of enzymes," Childers said. "Now that we understand that peptide membranes are organized locally like a protein, we want to investigate whether they can function like a protein."

The goal is to direct molecules to perform as catalysts and create long-range order. "We'd really like to understand how to build something from the bottom up," Childers says. "How can we take atoms and make molecules? How can we get molecules that stick together to make nano-machines that will perform specific tasks?"

The research is part of "The Center for Chemical Evolution," a center based at Emory and Georgia Tech, for integrated research, education and public outreach focused on the chemistry that may have led to the origin of life. The National Science Foundation and the U.S. Department of Energy have funded the research.

Many groups studying the origins of life have focused on RNA, which is believed to have pre-dated living cells. But RNA is a much more complicated molecule than a peptide. "Our studies have now shown that, if you just add water, simple peptides access both the physical properties and the long-range molecular order that is critical to the origins of chemical evolution," Childers says.

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How Dark Chocolate May Guard Against Brain Injury from Stroke

How Dark Chocolate May Guard Against Brain Injury from Stroke

  1:02:00 AM    Science Lover

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Researchers at Johns Hopkins have discovered that a compound in dark chocolate may protect the brain after a stroke by increasing cellular signals already known to shield nerve cells from damage.

A compound in dark chocolate may protect the brain 
after a stroke by increasing cellular signals already 
known to shield nerve cells from damage, new 
research shows. (Credit: iStockphoto/Lasse Kristensen)

Ninety minutes after feeding mice a single modest dose of epicatechin, a compound found naturally in dark chocolate, the scientists induced an ischemic stroke by essentially cutting off blood supply to the animals' brains. They found that the animals that had preventively ingested the epicatechin suffered significantly less brain damage than the ones that had not been given the compound.

While most treatments against stroke in humans have to be given within a two- to three-hour time window to be effective, epicatechin appeared to limit further neuronal damage when given to mice 3.5 hours after a stroke. Given six hours after a stroke, however, the compound offered no protection to brain cells.

Sylvain Doré, Ph.D., associate professor of anesthesiology and critical care medicine and pharmacology and molecular sciences at the Johns Hopkins University School of Medicine, says his study suggests that epicatechin stimulates two previously well-established pathways known to shield nerve cells in the brain from damage. When the stroke hits, the brain is ready to protect itself because these pathways -- Nrf2 and heme oxygenase 1 -- are activated. In mice that selectively lacked activity in those pathways, the study found, epicatechin had no significant protective effect and their brain cells died after a stroke.

The study now appears online in the Journal of Cerebral Blood Flow and Metabolism.

Eventually, Doré says, he hopes his research into these pathways could lead to insights into limiting acute stroke damage and possibly protecting against chronic neurological degenerative conditions, such as Alzheimer's disease and other age-related cognitive disorders.

The amount of dark chocolate people would need to consume to benefit from its protective effects remains unclear, since Doré has not studied it in clinical trials. People shouldn't take this research as a free pass to go out and consume large amounts of chocolate, which is high in calories and fat. In fact, people should be reminded to eat a healthy diet with a variety of fruits and vegetables.

Scientists have been intrigued by the potential health benefits of epicatechin by studying the Kuna Indians, a remote population living on islands off the coast of Panama. The islands' residents had a low incidence of cardiovascular disease. Scientists who studied them found nothing striking in the genes and realized that when they moved away from Kuna, they were no longer protected from heart problems. Researchers soon discovered the reason was likely environmental: The residents of Kuna regularly drank a very bitter cocoa drink, with a consistency like molasses, instead of coffee or soda. The drink was high in the compound epicatechin, which is a flavanol, a flavanoid-related compound.

But Doré says his research suggests the amount needed could end up being quite small because the suspected beneficial mechanism is indirect. "Epicatechin itself may not be shielding brain cells from free radical damage directly, but instead, epicatechin, and its metabolites, may be prompting the cells to defend themselves," he suggests.

The epicatechin is needed to jump-start the protective pathway that is already present within the cells. "Even a small amount may be sufficient," Doré says.

Not all dark chocolates are created equally, he cautions. Some have more bioactive epicatechin than others.

"The epicatechin found in dark chocolate is extremely sensitive to changes in heat and light" he says. "In the process of making chocolate, you have to make sure you don't destroy it. Only few chocolates have the active ingredient. The fact that it says 'dark chocolate' is not sufficient."

The new study was supported by grants from the National Institutes of Health and the American Heart and Stroke Association.

Other Johns Hopkins researchers on the study include Zahoor A. Shah, Ph.D.; Rung-chi Li, Ph.D.; Abdullah S. Ahmad, Ph.D.; Thomas W. Kensler, Ph.D.; and Shyam Biswal, Ph.D.

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Global Warming: Future Temperatures Could Exceed Livable Limits, Researchers Find

Global Warming: Future Temperatures Could Exceed Livable Limits, Researchers Find

  12:40:00 AM    Science Lover

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Reasonable worst-case scenarios for global warming could lead to deadly temperatures for humans in coming centuries, according to research findings from Purdue University and the University of New South Wales, Australia.

This map shows the maximum wet-bulb temperatures 
reached in a climate model from a high carbon dioxide 
emissions future climate scenario with a global-mean 
temperature 12 degrees Celsius (21 degrees Fahrenheit) 
warmer than 2007. The white land areas exceed the 
wet-bulb limit at which researchers calculated humans 
would experience a potentially lethal level of heat stress. 
(Credit: Purdue University graphic/Matthew Huber)

Researchers for the first time have calculated the highest tolerable "wet-bulb" temperature and found that this temperature could be exceeded for the first time in human history in future climate scenarios if greenhouse gas emissions continue at their current rate.

Wet-bulb temperature is equivalent to what is felt when wet skin is exposed to moving air. It includes temperature and atmospheric humidity and is measured by covering a standard thermometer bulb with a wetted cloth and fully ventilating it.

The researchers calculated that humans and most mammals, which have internal body temperatures near 98.6 degrees Fahrenheit, will experience a potentially lethal level of heat stress at wet-bulb temperature above 95 degrees sustained for six hours or more, said Matthew Huber, the Purdue professor of earth and atmospheric sciences who co-authored the paper that will be published in the Proceedings of the National Academy of Sciences.

"Although areas of the world regularly see temperatures above 100 degrees, really high wet-bulb temperatures are rare," Huber said. "This is because the hottest areas normally have low humidity, like the 'dry heat' referred to in Arizona. When it is dry, we are able to cool our bodies through perspiration and can remain fairly comfortable. The highest wet-bulb temperatures ever recorded were in places like Saudi Arabia near the coast where winds occasionally bring extremely hot, humid ocean air over hot land leading to unbearably stifling conditions, which fortunately are short-lived today."

The study did not provide new evaluations of the likelihood of future climate scenarios, but explored the impacts of warming. The challenges presented by the future climate scenarios are daunting in their scale and severity, he said.

"Whole countries would intermittently be subject to severe heat stress requiring large-scale adaptation efforts," Huber said. "One can imagine that such efforts, for example the wider adoption of air conditioning, would cause the power requirements to soar, and the affordability of such approaches is in question for much of the Third World that would bear the brunt of these impacts. In addition, the livestock on which we rely would still be exposed, and it would make any form of outside work hazardous."

While the Intergovernmental Panel on Climate Change central estimates of business-as-usual warming by 2100 are seven degrees Fahrenheit, eventual warming of 25 degrees is feasible, he said.

"We found that a warming of 12 degrees Fahrenheit would cause some areas of the world to surpass the wet-bulb temperature limit, and a 21-degree warming would put half of the world's population in an uninhabitable environment," Huber said. "When it comes to evaluating the risk of carbon emissions, such worst-case scenarios need to be taken into account. It's the difference between a game of roulette and playing Russian roulette with a pistol. Sometimes the stakes are too high, even if there is only a small chance of losing."

Steven Sherwood, the professor at the Climate Change Research Centre at the University of New South Wales, Australia, who is the paper's lead author, said prolonged wet-bulb temperatures above 95 degrees would be intolerable after a matter of hours.

"The wet-bulb limit is basically the point at which one would overheat even if they were naked in the shade, soaking wet and standing in front of a large fan," Sherwood said. "Although we are very unlikely to reach such temperatures this century, they could happen in the next."

Humans at rest generate about 100 watts of energy from metabolic activity. Wet-bulb temperature estimates provide upper limits on the ability of people to cool themselves by sweating and otherwise dissipating this heat, he said. In order for the heat dissipation process to work, the surrounding air must be cooler than the skin, which must be cooler than the core body temperature. The cooler skin is then able to absorb excess heat from the core and release it into the environment. If the wet-bulb temperature is warmer than the temperature of the skin, metabolic heat cannot be released and potentially dangerous overheating can ensue depending on the magnitude and duration of the heat stress.

The National Science Foundation-funded research investigated the long-term implications of sustained greenhouse gas emissions on climate extremes. The team used climate models to compare the peak wet-bulb temperatures to the global temperatures for various climate simulations and found that the peak wet-bulb temperature rises approximately 1 degree Centigrade for every degree Centigrade increase in tropical mean temperature.

Huber did the climate modeling on supercomputers operated by Information Technology at Purdue (ITaP), Purdue's central information technology organization. Sherwood performed the wet-bulb calculations.

"These temperatures haven't been seen during the existence of hominids, but they did occur about 50 million years ago, and it is a legitimate possibility that the Earth could see such temperatures again," Huber said. "If we consider these worst-case scenarios early enough, perhaps we can do something to address the risk through mitigation or new technological advancements that will allow us to adapt."

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Omni-Focus Video Camera to Revolutionize Industry: Automatic Real-Time Focus of Both Near and Far Field Images

Omni-Focus Video Camera to Revolutionize Industry: Automatic Real-Time Focus of Both Near and Far Field Images

  10:50:00 PM    Science Lover

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University of Toronto, a world-leading research university, announces a breakthrough development in video camera design. The Omni-focus Video Camera, based on an entirely new distance-mapping principle, delivers automatic real-time focus of both near and far field images, simultaneously, in high resolution. This unprecedented capability can be broadly applied in industry, including manufacturing, medicine, defense, security -- and for the consumer market.

The above figure illustrates the omni-focus 
video camera’s high pixel resolution. Although 
the two sewing needles were photographed 
approximately 1.2 meters apart, both are in 
sharp focus. Note the eye of the back needle,
is actually viewed through the eye of the front needle. 
(Credit: University of Toronto)

Inventor and principal investigator of the Omni-focus video camera, Professor Keigo Iizuka of The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, explains that, "the intensity of a point source decays with the inverse square of the distance of propagation. This variation with distance has proven to be large enough to provide depth mapping with high resolution. What's more, by using two point sources at different locations, the distance of the object can be determined without the influence of its surface texture." This principle led Professor Iizuka to invent a novel distance-mapping camera, the Divergence-ratio Axi-vision Camera, abbreviated "Divcam," which is a key component of the new Omni-focus Video Camera.

The Omni-focus Video Camera is produced in collaboration with consulting investigator Dr. David Wilkes, president of Wilkes Associates, a Canadian high-tech product development company. It contains an array of color video cameras, each focused at a different distance, and an integrated Divcam. The Divcam maps distance information for every pixel in the scene in real time. A software-based pixel correspondence utility, using prior intellectual property invented by Dr. Wilkes, then uses the distance information to select individual pixels from the ensemble of outputs of the color video cameras, and generates the final "omni-focused" single-video image.

"The Omni-focus Video Camera's unique ability to achieve simultaneous focus of all of the objects in a scene, near or far, multiple or single, without the usual physical movement of the camera's optics, represents a true advancement that is further distinguished in terms of high-resolution, distance mapping, real-time operation, simplicity, compactness, lightweight portability and a projected low manufacturing cost," says Dr. Wilkes.

The camera is still in the research phase. But it's not difficult to imagine how far-reaching an impact the Omni-focus Video Camera could have on several industries. As for the future direction of his research, Professor Iizuka sees the following possibilities:

1. Application of the Omni-focus Video Camera to TV studio cameras. Consider the example of a musical concert being televised by a major network. Even though the singer is in sharp focus, band members in the background, are invariably out of focus. Conventional video cameras are unable to focus simultaneously on both the singer and band members in the background. The Omni-focus Video Camera removes this limitation to deliver higher-quality video images and improved quality of experience to potentially millions of TV viewers, worldwide.
2. Application of the Omni-focus Video Camera to medicine. Says Professor Iizuka, "I'd like to apply the principle of the Omni-focus Video Camera to the design of a laparoscope. It would help doctors at the operating table, if they can see the entire view without touching optics of the laparoscope, especially if dealing with a large lesion."

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Microscope 'Sees' Atoms for First Time

Microscope 'Sees' Atoms for First Time

  9:16:00 PM    Science Lover

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UCLA researchers report in the April 30 edition of the journal Cell that they have imaged a virus structure at a resolution high enough to effectively "see" atoms, the first published instance of imaging biological complexes at such a resolution.

Cover of the journal Cell showing an artistic 
representation of a Cryo-EM 3-D reconstruction 
of an aquareovirus, the colors are added to show 
contrast between various structures in the virus. 
(Credit: Image courtesy of UCLA)

The research team, led by Hong Zhou, UCLA professor of microbiology, immunology and molecular genetics, used cryo-electron microscopy to image the structure at 3.3 angstroms. An angstrom is the smallest recognized division of a chemical element and is about the distance between the two hydrogen atoms in a water molecule.

The study, the researchers say, demonstrates the great potential of cryo-electron microscopy, or Cryo-EM, for producing extremely high-resolution images of biological samples in their native environment.

"This is the first study to determine an atomic resolution structure through Cryo-EM alone," said Xing Zhang, a postdoctoral candidate in Zhou's group and lead author of the Cell paper. "By proving the effectiveness of this microscopy technique, we have opened the door to a wide variety of biological studies."

With traditional light microscopy, a magnified image of a sample is viewed through a lens. Some samples, however, are too small to diffract visible light (in the 500 to 800 nm range, or 5,000 to 8,000 angstroms) and therefore cannot be seen. To image objects at the sub-500 nm scale, scientists must turn to other tools, such as atomic force microscopes, which use an atomically thin tip to generate an image by probing a surface, in much the same way a blind person reads by touching Braille lettering.

With electron microscopy, another sub-500 nm technology, a beam of electrons is fired at a sample, passing through empty areas and bouncing off dense areas. A digital camera reads the path of the electrons passing through the sample to create a two-dimensional projection image of the sample. By repeating this process at hundreds of different angles, a computer can construct a three-dimensional image of the sample at a very high resolution.

Zhou is faculty director of the Electron Imaging Center for Nanomachines (EICN) at UCLA's California NanoSystems Institute, which is using cryo-electron microscopy to create 3-D reconstructions of nano-machineries, nano-devices and biological nano-structures, such as viruses.

Structurally accurate 3-D reconstructions of biological complexes are possible with cryo-electron microscopy because the samples are flash frozen, which allows them to be imaged in their native environment, and the microscope operates in a vacuum, because electrons travel better in that environment. The Cell paper focused on a structural study of the aquareovirus, a non-envelope virus that causes disease in fish and shellfish, in an effort to better understand how non-envelope viruses infect host cells.

"We are extremely excited about the recent breakthrough achieved by Hong Zhou and his team at the EICN lab," said Leonard H. Rome, senior associate dean for research at the David Geffen School of Medicine at UCLA and associate director of the California NanoSystems Institute. "The ability to understand the structure of viruses at an atomic level will open avenues for manipulating them for use in drug delivery and propel numerous innovations in treatments of diseases. UCLA is fortunate to have such specialized instrumentation and the expertise of Professor Zhou and his team to take advantage of these marvelous microscopes."

Viruses can be classed into two types: envelope and non-envelope. Envelope viruses, which include influenza and HIV, are surrounded by an envelope-like membrane which the virus uses to fuse with and infect a host cell. Non-envelope viruses lack this membrane and instead use a protein to fuse with and infect cells. This process was poorly understood until Zhou's study.

"Through better knowledge of virus structures, we hope to engineer medications in three ways," Zhou said. "If we understand how viruses work, first we can identify small molecules or drugs that block their infection; second, we can engineer ultra-stable and non-infectious virus-like particles as optimal vaccines; and third, we can alter their characteristics so that instead of delivering a disease, viruses could deliver medications.

"Indeed, we are working with UCLA physicians and engineers to engineer viruses for gene therapy and drug delivery," he said. "In essence, we hope to take advantage of millions of years of evolution that have made viruses incredibly effective delivery platforms."

From the high-resolution 3-D images produced with the cryo-electron microscopy, Zhou's group was able to determine that the aquareovirus employs a priming stage to accomplish cell infection. In its dormant state, the virus has a protective protein covering, which it sheds during priming. Once the outer shell has been shed, the virus is in a primed state and is ready to use a protein called an "insertion finger" to infect a cell.

The team's study ushers in a new era of structural biology for understanding important biological processes. The group was able to discover this functionality because of the accurate structural model produced through cryo-electron microscopy. In addition to producing a high-resolution 3-D image of samples, the technology allows samples to be imaged in their native environment, so the structural model is faithful to the original sample. From a technical point of view, this work also demonstrates the power of cryo-electron microscopy in obtaining 3-D structures of biological complexes without needing to grow a crystal.

The California NanoSystems Institute at UCLA is an integrated research center operating jointly at UCLA and UC Santa Barbara whose mission is to foster interdisciplinary collaborations for discoveries in nanosystems and nanotechnology; train the next generation of scientists, educators and technology leaders; and facilitate partnerships with industry, fueling economic development and the social well-being of California, the United States and the world. The CNSI was established in 2000 with $100 million from the state of California and an additional $250 million in federal research grants and industry funding. At the institute, scientists in the areas of biology, chemistry, biochemistry, physics, mathematics, computational science and engineering are measuring, modifying and manipulating the building blocks of our world -- atoms and molecules. These scientists benefit from an integrated laboratory culture enabling them to conduct dynamic research at the nanoscale, leading to significant breakthroughs in the areas of health, energy, the environment and information technology.

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Renewable Energy: Inexpensive Metal Catalyst Can Effectively Generate Hydrogen from Water

Renewable Energy: Inexpensive Metal Catalyst Can Effectively Generate Hydrogen from Water

  11:55:00 PM    Science Lover

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Hydrogen would command a key role in future renewable energy technologies, experts agree, if a relatively cheap, efficient and carbon-neutral means of producing it can be developed. An important step towards this elusive goal has been taken by a team of researchers with the U.S. Department of Energy's (DOE) Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California, Berkeley. The team has discovered an inexpensive metal catalyst that can effectively generate hydrogen gas from water.

From left, Jeffrey Long, Christopher Chang and 
Hemamala Karunadasa have discovered an inexpensive 
metal that can generate hydrogen from neutral water, 
even if it is dirty, and can operate in sea water. 
(Credit: Photo by Roy Kaltschmidt, Berkeley Lab Public Affairs)

"Our new proton reduction catalyst is based on a molybdenum-oxo metal complex that is about 70 times cheaper than platinum, today's most widely used metal catalyst for splitting the water molecule," said Hemamala Karunadasa, one of the co-discoverers of this complex. "In addition, our catalyst does not require organic additives, and can operate in neutral water, even if it is dirty, and can operate in sea water, the most abundant source of hydrogen on earth and a natural electrolyte. These qualities make our catalyst ideal for renewable energy and sustainable chemistry."

Karunadasa holds joint appointments with Berkeley Lab's Chemical Sciences Division and UC Berkeley's Chemistry Department. She is the lead author of a paper describing this work that appears in the April 29, 2010 issue of the journal Nature, titled "A molecular molybdenum-oxo catalyst for generating hydrogen from water." Co-authors of this paper were Christopher Chang and Jeffrey Long, who also hold joint appointments with Berkeley Lab and UC Berkeley. Chang, in addition, is also an investigator with the Howard Hughes Medical Institute (HHMI).

Hydrogen gas, whether combusted or used in fuel cells to generate electricity, emits only water vapor as an exhaust product, which is why this nation would already be rolling towards a hydrogen economy if only there were hydrogen wells to tap. However, hydrogen gas does not occur naturally and has to be produced. Most of the hydrogen gas in the United States today comes from natural gas, a fossil fuel. While inexpensive, this technique adds huge volumes of carbon emissions to the atmosphere. Hydrogen can also be produced through the electrolysis of water -- using electricity to split molecules of water into molecules of hydrogen and oxygen. This is an environmentally clean and sustainable method of production -- especially if the electricity is generated via a renewable technology such as solar or wind -- but requires a water-splitting catalyst.

Nature has developed extremely efficient water-splitting enzymes -- called hydrogenases -- for use by plants during photosynthesis, however, these enzymes are highly unstable and easily deactivated when removed from their native environment. Human activities demand a stable metal catalyst that can operate under non-biological settings.

Metal catalysts are commercially available, but they are low valence precious metals whose high costs make their widespread use prohibitive. For example, platinum, the best of them, costs some $2,000 an ounce.

"The basic scientific challenge has been to create earth-abundant molecular systems that produce hydrogen from water with high catalytic activity and stability," Chang says. "We believe our discovery of a molecular molybdenum-oxo catalyst for generating hydrogen from water without the use of additional acids or organic co-solvents establishes a new chemical paradigm for creating reduction catalysts that are highly active and robust in aqueous media."

The molybdenum-oxo complex that Karunadasa, Chang and Long discovered is a high valence metal with the chemical name of (PY5Me2)Mo-oxo. In their studies, the research team found that this complex catalyzes the generation of hydrogen from neutral buffered water or even sea water with a turnover frequency of 2.4 moles of hydrogen per mole of catalyst per second.

Long says, "This metal-oxo complex represents a distinct molecular motif for reduction catalysis that has high activity and stability in water. We are now focused on modifying the PY5Me ligand portion of the complex and investigating other metal complexes based on similar ligand platforms to further facilitate electrical charge-driven as well as light-driven catalytic processes. Our particular emphasis is on chemistry relevant to sustainable energy cycles."

This research was supported in part by the DOE Office of Science through Berkeley Lab's Helios Solar Energy Research Center, and in part by a grant from the National science Foundation.

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