星空科学探索频道: 六月 2013

2013年6月28日星期五

Breakthrough in Internet bandwidth: New fiber optic technology could ease Internet congestion, video streaming

Described in the June 28 issue of the journal Science, the technology centers on donut-shaped laser light beams called optical vortices, in which the light twists like a tornado as it moves along the beam path, rather than in a straight line.

Widely studied in molecular biology, atomic physics and quantum optics, optical vortices (also known as orbital angular momentum, or OAM, beams) were thought to be unstable in fiber, until BU Engineering Professor Siddharth Ramachandran recently designed an optical fiber that can propagate them. In the paper, he and Alan Willner of USC demonstrate not only the stability of the beams in optical fiber but also their potential to boost Internet bandwidth.

"For several decades since optical fibers were deployed, the conventional assumption has been that OAM-carrying beams are inherently unstable in fibers," said Ramachandran. "Our discovery, of design classes in which they are stable, has profound implications for a variety of scientific and technological fields that have exploited the unique properties of OAM-carrying light, including the use of such beams for enhancing data capacity in fibers."

The reported research represents a close collaboration between optical fiber experts at BU and optical communication systems experts at USC. "Siddharth's fiber represents a very unique and valuable innovation. It was great to work together to demonstrate a terabit-per-second capacity transmission link," said Willner, electrical engineering professor at the USC Viterbi School of Engineering.

Ramachandran and Willner collaborated with OFS-Fitel, a fiber optics company in Denmark, and Tel Aviv University.

Funded by the Defense Advanced Research Projects Agency, the technology could not come at a better time, as one of the main strategies to boost Internet bandwidth is running into roadblocks just as mobile devices fuel rapidly growing demands on the Internet. Traditionally, bandwidth has been enhanced by increasing the number of colors, or wavelengths of data-carrying laser signals -- essentially streams of 1s and 0s -- sent down an optical fiber, where the signals are processed according to color. Increasing the number of colors has worked well since the 1990s when the method was introduced, but now that number is reaching physical limits.

An emerging strategy to boost bandwidth is to send the light through a fiber along distinctive paths, or modes, each carrying a cache of data from one end of the fiber to the other. Unlike the colors, however, data streams of 1s and 0s from different modes mix together; determining which data stream came from which source requires computationally intensive and energy-hungry digital signal processing algorithms.

Ramachandran's and Willner's approach combines both strategies, packing several colors into each mode, and using multiple modes. Unlike in conventional fibers, OAM modes in these specially designed fibers can carry data streams across an optical fiber while remaining separate at the receiving end. In experiments appearing in the Science paper, Ramachandran created an OAM fiber with four modes (an optical fiber typically has two), and he and Willner showed that for each OAM mode, they could send data through a one-kilometer fiber in 10 different colors, resulting in a transmission capacity of 1.6 terabits per second, the equivalent of transmitting eight Blu-RayTM DVDs every second.

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Prevailing view of how the brain is wired overturned?

June 27, 2013 — A series of studies conducted by Randy Bruno, PhD, and Christine Constantinople, PhD, of Columbia University's Department of Neuroscience, topples convention by showing that sensory information travels to two places at once: not only to the brain's mid-layer (where most axons lead), but also directly to its deeper layers. The study appears in the June 28, 2013, edition of the journal Science.

For decades, scientists have thought that sensory information is relayed from the skin, eyes, and ears to the thalamus and then processed in the six-layered cerebral cortex in serial fashion: first in the middle layer (layer 4), then in the upper layers (2 and 3), and finally in the deeper layers (5 and 6.) This model of signals moving through a layered "column" was largely based on anatomy, following the direction of axons -- the wires of the nervous system.

"Our findings challenge dogma," said Dr. Bruno, assistant professor of neuroscience and a faculty member at Columbia's new Mortimer B. Zuckerman Mind Brain Behavior Institute and the Kavli Institute for Brain Science. "They open up a different way of thinking about how the cerebral cortex does what it does, which includes not only processing sight, sound, and touch but higher functions such as speech, decision-making, and abstract thought."

The researchers used the well-understood sensory system of rat whiskers, which operate much like human fingers, providing tactile information about shape and texture. The system is ideal for studying the flow of sensory signals, said Dr. Bruno, because past research has mapped each whisker to a specific barrel-shaped cluster of neurons in the brain. "The wiring of these circuits is similar to those that process senses in other mammals, including humans," said Dr. Bruno.

The study relied on a sensitive technique that allows researchers to monitor how signals move across synapses from one neuron to the next in a live animal. Using a glass micropipette with a tip only 1 micron wide (one-thousandth of a millimeter) filled with fluid that conducts nerve signals, the researchers recorded nerve impulses resulting from whisker stimulation in 176 neurons in the cortex and 76 neurons in the thalamus. The recordings showed that signals are relayed from the thalamus to layers 4 and 5 at the same time. Although 80 percent of the thalamic axons went to layer 4, there was surprisingly robust signaling to the deeper layer.

To confirm that the deeper layer receives sensory information directly, the researchers used the local anesthetic lidocaine to block all signals from layer 4. Activity in the deeper layer remained unchanged.

"This was very surprising," said Dr. Constantinople, currently a postdoctoral researcher at Princeton University's Neuroscience Institute. "We expected activity in the lower layers to be turned off or very much diminished when we blocked layer 4. This raises a whole new set of questions about what the layers actually do."

The study suggests that upper and lower layers of the cerebral cortex form separate circuits and play separate roles in processing sensory information. Researchers think that the deeper layers are evolutionarily older -- they are found in reptiles, for example, while the upper and middle layers, appear in more evolved species and are thickest in humans.

One possibility, suggests Dr. Bruno, is that basic sensory processing is done in the lower layers: for example, visually tracking a tennis ball to coordinate the movement needed to make contact. Processing that involves integrating context or experience or that involves learning might be done in the upper layers. For example, watching where an opponent is hitting the ball and planning where to place the return shot.

"At this point, we still don't know what, behaviorally, the different layers do," said Dr. Bruno, whose lab is now focused on finding those answers.

Nobel-prize-winning neurobiologist Bert Sakmann, MD, PhD, of the Max Planck Institute in Germany, describes the study as "very convincing" and a game-changer. "For decades, the field has assumed, based largely on anatomy, that the work of the cortex begins in layer 4. Dr. Bruno has produced a technical masterpiece that firmly establishes two separate input streams to the cortex," said Dr. Sakmann. "The prevailing view that the cortex is a collection of monolithic columns, handing off information to progressively higher modules, is an idea that will have to go."

"Bruno's work goes a long way toward overturning the conventional wisdom and provides new insight into the functional segregation of sensory input to the mammalian cerebral cortex, the region of the brain that processes our thoughts, decisions, and actions," said Thomas Jessell, PhD, Claire Tow Professor of Motor Neuron Disorders in Neuroscience and a co-director of the Mortimer B. Zuckerman Mind Brain Behavior Institute and the Kavli Institute for Brain Science. "Developing a more refined understanding of cortical processing will take the combined efforts of anatomists, cell and molecular biologists, and animal behaviorists. The Zuckerman Institute, with its multidisciplinary faculty and broad mission, is ideally suited to building on Bruno's fascinating work."

Funding for the study was provided by the National Institute of Neurological Disorders and Stroke (Grant # NS069679), the Rita Allen Foundation, and the Klingenstein Fund.

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Imagination can change what we hear and see

June 27, 2013 — A study from Karolinska Institutet in Sweden shows, that our imagination may affect how we experience the world more than we perhaps think. What we imagine hearing or seeing "in our head" can change our actual perception. The study, which is published in the scientific journal Current Biology, sheds new light on a classic question in psychology and neuroscience -- about how our brains combine information from the different senses.

"We often think about the things we imagine and the things we perceive as being clearly dissociable," says Christopher Berger, doctoral student at the Department of Neuroscience and lead author of the study. "However, what this study shows is that our imagination of a sound or a shape changes how we perceive the world around us in the same way actually hearing that sound or seeing that shape does. Specifically, we found that what we imagine hearing can change what we actually see, and what we imagine seeing can change what we actually hear."

The study consists of a series of experiments that make use of illusions in which sensory information from one sense changes or distorts one's perception of another sense. Ninety-six healthy volunteers participated in total.

In the first experiment, participants experienced the illusion that two passing objects collided rather than passed by one-another when they imagined a sound at the moment the two objects met. In a second experiment, the participants' spatial perception of a sound was biased towards a location where they imagined seeing the brief appearance of a white circle. In the third experiment, the participants' perception of what a person was saying was changed by their imagination of a particular sound.

According to the scientists, the results of the current study may be useful in understanding the mechanisms by which the brain fails to distinguish between thought and reality in certain psychiatric disorders such as schizophrenia. Another area of use could be research on brain computer interfaces, where paralyzed individuals' imagination is used to control virtual and artificial devices.

"This is the first set of experiments to definitively establish that the sensory signals generated by one's imagination are strong enough to change one's real-world perception of a different sensory modality" says Professor Henrik Ehrsson, the principle investigator behind the study.

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Microsoft Build: From Windows 8.1 to Xbox

As promised, Microsoft on Wednesday launched a public preview of Windows 8.1. Speaking to a developer-heavy audience of 5,000, CEO Steve Ballmer introduced the update during the opening keynote at the company's Build conference in San Francisco. The venue demanded attention not only to Win8, whose Modern UI has been the subject of much criticism and debate, but also to the wider Microsoft ecosystem to which developers now have access. Ballmer and other execs largely met this dual mandate by making Win8.1 one of only several major topics discussed throughout the keynote.

Other focuses included opening Bing as a development platform, empowering developers with new tools and creating a cohesive experience across the Windows ecosystem, from smartphones to desktops.

Click to read the rest of this story on InformationWeek.

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NASA's Voyager 1 explores final frontier of our 'solar bubble'

June 27, 2013 — Data from Voyager 1, now more than 11 billion miles (18 billion kilometers) from the sun, suggest the spacecraft is closer to becoming the first human-made object to reach interstellar space.

Research using Voyager 1 data and published in the journal Science today provides new detail on the last region the spacecraft will cross before it leaves the heliosphere, or the bubble around our sun, and enters interstellar space. Three papers describe how Voyager 1's entry into a region called the magnetic highway resulted in simultaneous observations of the highest rate so far of charged particles from outside heliosphere and the disappearance of charged particles from inside the heliosphere.

Scientists have seen two of the three signs of interstellar arrival they expected to see: charged particles disappearing as they zoom out along the solar magnetic field, and cosmic rays from far outside zooming in. Scientists have not yet seen the third sign, an abrupt change in the direction of the magnetic field, which would indicate the presence of the interstellar magnetic field.

"This strange, last region before interstellar space is coming into focus, thanks to Voyager 1, humankind's most distant scout," said Ed Stone, Voyager project scientist at the California Institute of Technology in Pasadena. "If you looked at the cosmic ray and energetic particle data in isolation, you might think Voyager had reached interstellar space, but the team feels Voyager 1 has not yet gotten there because we are still within the domain of the sun's magnetic field."

Scientists do not know exactly how far Voyager 1 has to go to reach interstellar space. They estimate it could take several more months, or even years, to get there. The heliosphere extends at least 8 billion miles (13 billion kilometers) beyond all the planets in our solar system. It is dominated by the sun's magnetic field and an ionized wind expanding outward from the sun. Outside the heliosphere, interstellar space is filled with matter from other stars and the magnetic field present in the nearby region of the Milky Way.

Voyager 1 and its twin spacecraft, Voyager 2, were launched in 1977. They toured Jupiter, Saturn, Uranus and Neptune before embarking on their interstellar mission in 1990. They now aim to leave the heliosphere. Measuring the size of the heliosphere is part of the Voyagers' mission.

The Science papers focus on observations made from May to September 2012 by Voyager 1's cosmic ray, low-energy charged particle and magnetometer instruments, with some additional charged particle data obtained through April of this year.

Voyager 2 is about 9 billion miles (15 billion kilometers) from the sun and still inside the heliosphere. Voyager 1 was about 11 billion miles (18 billion kilometers) from the sun Aug. 25 when it reached the magnetic highway, also known as the depletion region, and a connection to interstellar space. This region allows charged particles to travel into and out of the heliosphere along a smooth magnetic field line, instead of bouncing around in all directions as if trapped on local roads. For the first time in this region, scientists could detect low-energy cosmic rays that originate from dying stars.

"We saw a dramatic and rapid disappearance of the solar-originating particles. They decreased in intensity by more than 1,000 times, as if there was a huge vacuum pump at the entrance ramp onto the magnetic highway," said Stamatios Krimigis, the low-energy charged particle instrument's principal investigator at the Johns Hopkins University Applied Physics Laboratory in Laurel, Md. "We have never witnessed such a decrease before, except when Voyager 1 exited the giant magnetosphere of Jupiter, some 34 years ago."

Other charged particle behavior observed by Voyager 1 also indicates the spacecraft still is in a region of transition to the interstellar medium. While crossing into the new region, the charged particles originating from the heliosphere that decreased most quickly were those shooting straightest along solar magnetic field lines. Particles moving perpendicular to the magnetic field did not decrease as quickly. However, cosmic rays moving along the field lines in the magnetic highway region were somewhat more populous than those moving perpendicular to the field. In interstellar space, the direction of the moving charged particles is not expected to matter.

In the span of about 24 hours, the magnetic field originating from the sun also began piling up, like cars backed up on a freeway exit ramp. But scientists were able to quantify that the magnetic field barely changed direction -- by no more than 2 degrees.

"A day made such a difference in this region with the magnetic field suddenly doubling and becoming extraordinarily smooth," said Leonard Burlaga, the lead author of one of the papers, and based at NASA's Goddard Space Flight Center in Greenbelt, Md. "But since there was no significant change in the magnetic field direction, we're still observing the field lines originating at the sun."

NASA's Jet Propulsion Laboratory, in Pasadena, Calif., built and operates the Voyager spacecraft. California Institute of Technology in Pasadena manages JPL for NASA. The Voyager missions are a part of NASA's Heliophysics System Observatory, sponsored by the Heliophysics Division of the Science Mission Directorate at NASA Headquarters in Washington.

For more information about the Voyager spacecraft mission, visit: http://www.nasa.gov/voyager and http://voyager.jpl.nasa.gov .

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Scientists discover thriving colonies of microbes in ocean 'plastisphere'

In a study recently published online in Environmental Science & Technology, the scientists say the plastisphere represents a novel ecological habitat in the ocean and raises a host of questions: How will it change environmental conditions for marine microbes, favoring some that compete with others? How will it change the overall ocean ecosystem and affect larger organisms? How will it change where microbes, including pathogens, will be transported in the ocean?

The collaborative team of scientists -- Erik Zettler from Sea Education Association (SEA), Tracy Mincer from Woods Hole Oceanographic Institution (WHOI), and Linda Amaral-Zettler from the Marine Biological Laboratory (MBL), all in Woods Hole, Mass. -- analyzed marine plastic debris that was skimmed with fine-scale nets from the sea surface at several locations in the North Atlantic Ocean during SEA research cruises. Most were millimeter-sized fragments.

"We're not just interested in who's there. We're interested in their function, how they're functioning in this ecosystem, how they're altering this ecosystem, and what's the ultimate fate of these particles in the ocean," says Amaral-Zettler. "Are they sinking to the bottom of the ocean? Are they being ingested? If they're being ingested, what impact does that have?"

Using scanning electron microscopy and gene sequencing techniques, they found at least 1000 different types of bacterial cells on the plastic samples, including many individual species yet to be identified. They included plants, algae, and bacteria that manufacture their own food (autotrophs), animals and bacteria that feed on them (heterotrophs), predators that feed on these, and other organisms that establish synergistic relationships (symbionts). These complex communities exist on plastic bits hardly bigger than the head of a pin, and they have arisen with the explosion of plastics in the oceans in the last 60 years.

"The organisms inhabiting the plastisphere were different from those in surrounding seawater, indicating that plastic debris acts as artificial 'microbial reefs," says Mincer. "They supply a place that selects for and supports distinct microbes to settle and succeed."

These communities are likely different from those that settle on naturally occurring floating material such as feathers, wood, and microalgae, because plastics offer different conditions, including the capacity to last much longer without degrading.

On the other hand, the scientists also found evidence that microbes may play a role in degrading plastics. They saw microscopic cracks and pits in the plastic surfaces that they suspect were made by microbes embedded in them, as well as microbes possibly capable of degrading hydrocarbons.

"When we first saw the 'pit formers' we were very excited, especially when they showed up on multiple pieces of plastic of different types of resins," said Zettler, who added that undergraduate students participating in SEA Semester cruises collected and processed the samples. "Now we have to figure out what they are by [genetically] sequencing them and hopefully getting them into culture so we can do experiments."

The plastic debris also represents a new mode of transportation, acting as rafts that can convey harmful microbes, including disease-causing pathogens and harmful algal species. One plastic sampled they analyzed was dominated by members of the genus Vibrio, which includes bacteria that cause cholera and gastrointestinal maladies.

The project was funded by a National Science Foundation Collaborative grant, a NSF TUES grant, and a Woods Hole Center for Oceans and Human Health Pilot award.

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2013年6月27日星期四

Hold the medicinal lettuce

June 26, 2013 — In 2011 and 2012, research from China's Nanjing University made international headlines with reports that after mice ate, bits of genetic material from the plants they'd ingested could make it into their bloodstreams intact and turn the animals' own genes off. The surprising results from Chen-Yu Zhang's group led to speculation that genetic illness might one day be treated with medicinal food, but also to worry that genetically modified foods might in turn modify consumers in unanticipated ways.

Now, though, a research team at Johns Hopkins reports that Zhang's results were likely a false positive that resulted from the technique his group used. The new study, the Johns Hopkins group says, bolsters the case of skeptics who argued that genetic material from food would have little chance of surviving the digestive system, much less crossing the intestinal lining to enter the bloodstream. The study appears in the July issue of RNA Biology.

"It's disappointing in a sense -- it would open up so many therapeutic possibilities if microRNAs from food really could get into our blood and regulate our genes," says Kenneth Witwer, Ph.D., of the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences, who led the new study. But beyond the fact that people won't be picking up prescription lettuce at the pharmacy anytime soon, he adds, the larger lesson is that scientific research's capacity for self-correction is alive and well.

Witwer said his group was intrigued by the earlier results, in which Zhang's group focused on microRNAs, molecules that are a chemical cousin of DNA. Rather than storing genetic information as DNA does, their primary role is to intervene in so-called "gene expression," the process of using genes' blueprints to build proteins. Because they affect whether and how much genes are actually used, microRNAs wield tremendous power, Witwer notes, "so it was startling to think that microRNAs from plants could get into the bloodstream, get into tissues, and regulate genes in those tissues."

Witwer teamed up with colleagues to check the results with a similar experiment of their own. They bought soy-based smoothies at a grocery store and tested their microRNA content, then fed the smoothies to macaques and took samples of the animals' blood.

Knowing that the concentrations of any plant microRNAs in the blood would be too low to measure directly, they used a common technique called polymerase chain reaction (PCR) to bring up the concentration of the genetic material. PCR is designed so that only certain fragments of genetic material in a sample -- the ones researchers choose to target -- will be copied. Zhang's studies had also used PCR to look for plant microRNAs.

Just as Zhang had, the Johns Hopkins team found what appeared to be the targeted plant microRNAs in the macaques' blood. But when they ran the experiment several times, they got highly variable results: Sometimes the microRNAs were present in low concentrations, and sometimes not at all. In addition, the samples from before the macaques drank the smoothies were just as likely to have the microRNAs as were the post-smoothie samples -- a result that just didn't make sense if the source of the microRNAs was the plant material in the drinks.

To Witwer, the results indicated that what he was seeing was not the targeted plant microRNAs, but fragments of the macaques' own genetic material that were similar enough to the targeted segments that the PCR copied them at low levels.

To test this, the team used a new technique in which PCR takes place in tiny aerosolized droplets rather than in a test tube. The advantage, Witwer says, is that by effectively running tens or hundreds of thousands of reactions at the same time, researchers can see whether the outcomes of those reactions are consistent -- in other words, whether the results are meaningful or just a fluke. In this case, the results were all over the place, indicating that plant microRNAs weren't really present.

At the same time, Witwer cautions, it remains possible that very low levels of microRNAs could enter the blood. Even if this happened, though, he says it is unlikely that such small numbers of molecules could affect gene expression. Additional studies will be needed to determine whether low-level transfer occurs and whether any plant RNAs serve a function in the body.

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First transiting planets in a star cluster discovered

It would thus seem an unlikely place to find alien worlds. Yet 3,000 light-years from Earth, in the star cluster NGC 6811, astronomers have found two planets smaller than Neptune orbiting Sun-like stars. The discovery, published in the journal Nature, shows that planets can develop even in crowded clusters jam-packed with stars.

"Old clusters represent a stellar environment much different than the birthplace of the Sun and other planet-hosting field stars," says lead author Soren Meibom of the Harvard-Smithsonian Center for Astrophysics (CfA). "And we thought maybe planets couldn't easily form and survive in the stressful environments of dense clusters, in part because for a long time we couldn't find them."

The two new alien worlds appeared in data from NASA's Kepler spacecraft. Kepler hunts for planets that transit, or cross in front of, their host stars. During a transit, the star dims by an amount that depends on the size of the planet, allowing the size to be determined. Kepler-66b and Kepler-67b are both less than three times the size of Earth, or about three-fourths the size of Neptune (mini-Neptunes).

Of the more than 850 known planets beyond our solar system, only four -- all similar to or greater than Jupiter in mass -- were found in clusters. Kepler-66b and -67b are the smallest planets to be found in a star cluster, and the first cluster planets seen to transit their host stars, which enables the measurement of their sizes.

Meibom and his colleagues have measured the age of NGC 6811 to be one billion years. Kepler-66b and Kepler-67b therefore join a small group of planets with precisely determined ages, distances, and sizes.

Considering the number of stars observed by Kepler in NGC 6811, the detection of two such planets implies that the frequency and properties of planets in open clusters are consistent with those of planets around field stars (stars not within a cluster or association) in the Milky Way galaxy.

"These planets are cosmic extremophiles," says Meibom. "Finding them shows that small planets can form and survive for at least a billion years, even in a chaotic and hostile environment."

Headquartered in Cambridge, Mass., the Harvard-Smithsonian Center for Astrophysics (CfA) is a joint collaboration between the Smithsonian Astrophysical Observatory and the Harvard College Observatory. CfA scientists, organized into six research divisions, study the origin, evolution and ultimate fate of the universe.

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Human activities threaten Sumatran tiger population

Virginia Tech and World Wildlife Fund researchers have found that tigers in central Sumatra live at very low densities, lower than previously believed, according to a study in the April 2013 issue of Oryx -- The International Journal of Conservation.

The findings by Sunarto, who earned his doctorate from Virginia Tech in 2011, and co-researchers Marcella Kelly, an associate professor of wildlife in the College of Natural Resources and Environment, and Erin Poor of East Lansing, Mich., a doctoral student studying wildlife science and geospatial environmental analysis in the college, suggest that high levels of human activity limit the tiger population.

Researchers studied areas and habitat types not previously surveyed, which could inform interventions needed to save the tiger.

"Tigers are not only threatened by habitat loss from deforestation and poaching; they are also very sensitive to human disturbance," said Sunarto, a native of Indonesia, where people typically have one name. "They cannot survive in areas without adequate understory, but they are also threatened in seemingly suitable forests when there is too much human activity."

The smallest surviving tiger subspecies, Sumatran tigers are extremely elusive and may live at densities as low as one cat per 40 square miles. This is the first study to compare the density of Sumatran tigers across various forest types, including the previously unstudied peat land. The research applied spatial estimation techniques to provide better accuracy of tiger density than previous studies.

Sunarto, a tiger and elephant specialist with World Wildlife Fund-Indonesia, collaborated on the paper with Kelly, Professor Emeritus Michael Vaughan, and Sybille Klenzendorf, managing director of WWF's Species Conservation Program, who earned her master's and doctoral degrees in wildlife science from Virginia Tech. The WWF field team collected data in partnership with the Indonesian Ministry of Forestry staff.

"Getting evidence of the tigers' presence was difficult," Kelly said. "It took an average of 590 days for camera traps to get an image of each individual tiger recorded."

"We believe the low detection of tigers in the study area of central Sumatra was a result of the high level of human activity -- farming, hunting, trapping, and gathering of forest products," Sunarto said. "We found a low population of tigers in these areas, even when there was an abundance of prey animals."

Legal protection of an area, followed by intensive management, can reduce the level of human disturbance and facilitate the recovery of the habitat and as well as tiger numbers. The researchers documented a potentially stable tiger population in the study region's Tesso Nilo Park, where legal efforts are in place to discourage destructive human activities.

The study -- "Threatened predator on the equator: Multi-point abundance estimates of the tiger Panthera tigris in central Sumatra" -- indicates that more intensive monitoring and proactive management of tiger populations and their habitats are crucial or this tiger subspecies will soon follow the fate of its extinct Javan and Balinese relatives.

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Simple two-drug combination proves effective in reducing risk of stroke

June 26, 2013 — Results of a Phase III clinical trial showed that a simple drug regimen of two anti-clotting drugs -- clopidogrel and aspirin -- lowered the risk of stroke by almost one-third, compared to the standard therapy of aspirin alone, when given to patients who had minor or transient stroke symptoms to prevent subsequent attacks.

Described this week in the New England Journal of Medicine (July 4, 2013 print issue), the clinical trial was conducted at multiple sites in China and designed in partnership with a physician at UC San Francisco.

The trial involved 5,170 people who were hospitalized after suffering minor ischemic strokes or stroke-like events known as transient ischemic attacks, or TIAs, in which blood flow to the brain is briefly blocked. All patients were randomized into two groups and treated for three months with either aspirin alone or aspirin plus clopidogrel, which is marketed as Plavix. The three-month period following stroke is considered the most critical for medical intervention.

Overall, 8.2 percent of patients taking both drugs suffered subsequent strokes in the three months of follow-up compared to 11.7 percent of patients taking aspirin alone.

"The results were striking," said S. Claiborne Johnston, MD, PhD, a professor of neurology and associate vice chancellor of research at UCSF who was a senior author on the study.

The Chinese trial, called CHANCE (Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events), is nearly identical to a National Institutes of Health-sponsored trial that is already enrolling patients in the United States, including at UCSF, called POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke).

"If POINT confirms CHANCE, then we're done -- the two-drug combination becomes the standard of care," said Johnston. "Anybody with a transient ischemic attack or minor stroke will get clopidogrel plus aspirin."

The POINT trial is important, said Johnston, because genetics, risk factors, and medical practice differences could all lead to differences in trial results in China compared to other countries. Johnston is the principal investigator of the POINT trial.

Stroke in China and the United States

Stroke is a leading cause of death and disability worldwide and is the fourth leading cause of death in the United States.

More than 795,000 people in the United States have strokes every year, and, in 2008 alone, some 133,000 cases were fatal, according to the U.S. Centers for Disease Control and Prevention. Another 300,000 people in the United States have TIAs each year.

Many strokes are minor -- shorter in duration than a full-blown stroke and usually have no lingering health impacts. In China, for instance, about 3 million new strokes occur every year, and about 30 percent of them are minor.

The protocol for the CHANCE trial was developed by Johnston and colleagues at Tiantan Hospital in China. The lead author of the study was Yongjun Wang, MD, of Beijing Tiantan Hospital.

China has many times more people who have strokes every year than the United States because of the size of the population and higher stroke rates, which allowed investigators to screen 41,561 patients in just three years at the 114 clinical sites, and enroll 5,170 patients in the trial.

Increased Risk of Subsequent Stroke

The reason for minor attacks is much the same as a full-blown stroke: a blood clot causes a blockage in the blood vessels that feed oxygen-rich blood to the brain. But in patients with TIAs and many minor strokes, the clot quickly goes away, usually in a few minutes, due to the natural mechanisms in the human body that are designed to deal with such clots.

However, in the weeks following a TIA or minor stroke, there is great risk that another clot will form, causing additional strokes -- potentially major ones. About 10 to 20 percent of people who have a TIA or minor stroke go on to have a subsequent stroke within three months.

Because of this risk, the first 90 days after a stroke or TIA is the most critical window for medical intervention. Currently, people who have minor strokes or TIAs are initially treated with aspirin alone. The purpose of the CHANCE trial was to determine whether clopidogrel with aspirin was more effective than aspirin alone in this intervention.

The drugs basically work the same way. They are "antiplatelet" agents, which target clotting agents found in the bloodstream know as platelets, preventing their aggregation. The combination is used commonly in patients who have heart attacks, but there has been no adequate clinical data to suggest it would work in stroke.

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