Complex Logic Circuit from Bacterial Genes

Complex Logic Circuit from Bacterial Genes

  11:34:00 AM    Science Lover

---

By force of habit we tend to assume computers are made of silicon, but there is actually no necessary connection between the machine and the material. All that an engineer needs to do to make a computer is to find a way to build logic gates -- the elementary building blocks of digital computers -- in whatever material is handy.

Just as electronic circuits are made from resistors, capacitors 
and transistors, biological circuits can be made from genes 
and regulatory proteins. Engineer Tae Seok Moon’s dream is 
to design modular “genetic parts” that can be used to build 
logic controllers inside microbes that will program them to 
make fuel, clean up pollutants, or kill infectious bacteria 
or cancerous cells. (Credit: © madarakis / Fotolia)

So logic gates could theoretically be made of pipes of water, channels for billiard balls or even mazes for soldier crabs.

By comparison Tae Seok Moon's ambition, which is to build logic gates out of genes, seems eminently practical. As a postdoctoral fellow in the lab of Christopher Voigt, PhD, a synthetic biologist at the Massachusetts Institute of Technology, he recently made the largest gene (or genetic) circuit yet reported.

Moon, PhD, now an assistant professor of energy, environmental and chemical engineering in the School of Engineering & Applied Science at Washington University in St. Louis is the lead author of an article describing the project in the Oct. 7 issue of Nature. Voigt is the senior author.

The tiny circuits constructed from these gene gates and others like them may one day be components of engineered cells that will monitor and respond to their environments.

The number of tasks they could undertake is limited only by evolution and human ingenuity. Janitor bacteria might clean up pollutants, chemical-engineer bacteria pump out biofuels and miniature infection-control bacteria might bustle about killing pathogens.

How to make an AND gate out of genes

The basis of modern computers is the logic gate, a device that makes simple comparisons between the bits, the 1s and 0s, in which computers encode information. Each logic gate has multiple inputs and one output. The output of the gate depends on the inputs and the operation the gate performs.

An AND gate, for example, turns on only if all of its inputs are on. An OR gate turns on if any of its inputs are on.

Suggestively, genes are turned on or off when a transcription factor binds to a region of DNA adjacent to the gene called a promotor.

To make an AND gate out of genes, however, Moon had to find a gene whose activation is controlled by at least two molecules, not one. So only if both molecule 1 AND molecule 2 are present will the gene be turned on and translated into protein.

Such a genetic circuit had been identified in Salmonella typhimurium, the bacterium that causes food poisoning. In this circuit, the transcription factor can bind to the promotor of a gene only if a molecule called a chaperone is present. This meant the genetic circuit could form the basis of a two-input AND gate.

The circuit Moon eventually built consisted of four sensors for four different molecules that fed into three two-input AND gates. If all four molecules were present, all three AND gates turned on and the last one produced a reporter protein that fluoresced red, so that the operation of the circuit could be easily monitored.

In the future, Moon says, a synthetic bacterium with this circuit might sense four different cancer indicators and, in the presence of all four, release a tumor-killing factor.

Crosstalk and timing faults

There are huge differences, of course, between the floppy molecules that embody biological logic gates and the diodes and transistors that embody electronic ones.

Engineers designing biological circuits worry a great deal about crosstalk, or interference. If a circuit is to work properly, the molecules that make up one gate cannot bind to molecules that are part of another gate.

This is much more of a problem in a biological circuit than in an electronic circuit because the interior of a cell is a kind of soup where molecules mingle freely.

To ensure that there wouldn't be crosstalk among his AND gates, Moon mined parts for his gates from three different strains of bacteria: Shigella flexneri and Pseudomonas aeruginosa, as well as Salmonella.

Although the parts from the three different strains were already quite dissimilar, he made them even more so by subjecting them to error-prone copying cycles and screening the copies for ones that were even less prone to crosstalk (but still functional).

Another problem Moon faced is that biological circuits, unlike electronic ones, don't have internal clocks that keep the bits moving through the logic gates in lockstep. If signals progress through layers of gates at different speeds, the output of the entire circuit may be wrong, a problem called a timing fault.

Experiments designed to detect such faults in the synthetic circuit showed that they didn't occur, probably because the chaperones for one layer of logic gates degrades before the transcription factors for the next layer are generated, and this forces a kind of rhythm on the circuit.

Hijacking a bacterium's controller

"We're not trying to build a computer out of biological logic gates," Moon says. "You can't build a computer this way. Instead we're trying to make controllers that will allow us to access all the things biological organisms do in simple, programmable ways."

"I see the cell as a system that consists of a sensor, a controller (the logic circuit), and an actuator," he says. "This paper covers work on the controller, but eventually the controller's output will drive an actuator, something that will do work on the cell's surroundings. "

An synthetic bacterium designed by a friend of Moon's at Nanyang Technological University in Singapore senses signaling molecules released by the pathogen Pseudomonas aeruginosa. When the molecules reach a high enough concentration, the bacterium generates a toxin and a protein that causes it to burst, releasing the toxin, and killing nearby P. aeruginosa.

"Silicon cannot do that," Moon says.

Read More

'Invisibility': Key to Better Electronics?

'Invisibility': Key to Better Electronics?

  11:07:00 AM    Science Lover

---

Visual 'Cloaking' Technology Enables More Efficient Transfer of Electrons

 A new approach that allows objects to become "invisible" has now been applied to an entirely different area: letting particles "hide" from passing electrons, which could lead to more efficient thermoelectric devices and new kinds of electronics.

Diagram shows the 'probability flux' of electrons, a 
representation of the paths of electrons as they pass through 
an 'invisible' nanoparticle. While the paths are bent as 
they enter the particle, they are subsequently bent back 
so that they re-emerge from the other side on the same 
trajectory they started with — just as if the particle 
wasn't there. (Credit: Image courtesy Bolin Liao et al.)

The concept -- developed by MIT graduate student Bolin Liao, former postdoc Mona Zebarjadi (now an assistant professor at Rutgers University), research scientist Keivan Esfarjani, and mechanical engineering professor Gang Chen -- is described in a paper in the journal Physical Review Letters.

Normally, electrons travel through a material in a way that is similar to the motion of electromagnetic waves, including light; their behavior can be described by wave equations. That led the MIT researchers to the idea of harnessing the cloaking mechanisms developed to shield objects from view -- but applying it to the movement of electrons, which is key to electronic and thermoelectric devices.

Previous work on cloaking objects from view has relied on so-called metamaterials made of artificial materials with unusual properties. The composite structures used for cloaking cause light beams to bend around an object and then meet on the other side, resuming their original path -- making the object appear invisible.

"We were inspired by this idea," says Chen, the Carl Richard Soderberg Professor of Power Engineering at MIT, who decided to study how it might apply to electrons instead of light. But in the new electron-cloaking material developed by Chen and his colleagues, the process is slightly different.

The MIT researchers modeled nanoparticles with a core of one material and a shell of another. But in this case, rather than bending around the object, the electrons do actually pass through the particles: Their paths are bent first one way, then back again, so they return to the same trajectory they began with.

In computer simulations, the concept appears to work, Liao says. Now, the team will try to build actual devices to see whether they perform as expected. "This was a first step, a theoretical proposal," Liao says. "We want to carry on further research on how to make some real devices out of this strategy."

While the initial concept was developed using particles embedded in a normal semiconductor substrate, the MIT researchers would like to see if the results can be replicated with other materials, such as two-dimensional sheets of graphene, which might offer interesting additional properties.

The MIT researchers' initial impetus was to optimize the materials used in thermoelectric devices, which produce an electrical current from a temperature gradient. Such devices require a combination of characteristics that are hard to obtain: high electrical conductivity (so the generated current can flow freely), but low thermal conductivity (to maintain a temperature gradient). But the two types of conductivity tend to coexist, so few materials offer these contradictory characteristics. The team's simulations show this electron-cloaking material could meet these requirements unusually well.

The simulations used particles a few nanometers in size, matching the wavelength of flowing electrons and improving the flow of electrons at particular energy levels by orders of magnitude compared to traditional doping strategies. This might lead to more efficient filters or sensors, the researchers say. As the components on computer chips get smaller, Chen says, "we have to come up with strategies to control electron transport," and this might be one useful approach.

The concept could also lead to a new kind of switches for electronic devices, Chen says. The switch could operate by toggling between transparent and opaque to electrons, thus turning a flow of them on and off. "We're really just at the beginning," he says. "We're not sure how far this is going to go yet, but there is some potential" for significant applications.

Xiang Zhang, a professor of mechanical engineering at the University of California at Berkeley who was not involved in this research, says "this is very exciting work" that expands the concept of cloaking to the domain of electrons. The authors, he says, "uncovered a very interesting approach that may be very useful to thermoelectric applications."

This research was funded by the U.S. Department of Energy (DOE) through MIT's Solid-State Solar-Thermal Energy Conversion center, a DOE Energy Frontier Research Center.

Read More

Gravity Lenses: When Galaxies Eat Galaxies

Gravity Lenses: When Galaxies Eat Galaxies

  9:44:00 AM    Science Lover

---

Using gravitational "lenses" in space, University of Utah astronomers discovered that the centers of the biggest galaxies are growing denser -- evidence of repeated collisions and mergers by massive galaxies with 100 billion stars.

This image, taken by the Hubble Space Telescope, shows 
a ring of light from a distant galaxy created when a closer 
galaxy in the  foreground – not shown in this processed 
image – acts as a “gravitational lens” to bend the light 
from the more distant galaxy into the ring of light, 
known as an Einstein ring. In a new study, University of 
Utah astronomer Adam Bolton and colleagues measured 
these Einstein rings to determine the mass of 79 lens 
galaxies that are massive elliptical galaxies, the largest 
kind of galaxy with 100 billion stars. The study found 
the centers of these big galaxies are getting denser over 
time, evidence of repeated collisions between massive 
galaxies. (Credit: Joel Brownstein, University of Utah, 
for NASA/ESA and the Sloan Digital Sky Survey)

"We found that during the last 6 billion years, the matter that makes up massive elliptical galaxies is getting more concentrated toward the centers of those galaxies. This is evidence that big galaxies are crashing into other big galaxies to make even bigger galaxies," says astronomer Adam Bolton, principal author of the new study.

"Most recent studies have indicated that these massive galaxies primarily grow by eating lots of smaller galaxies," he adds. "We're suggesting that major collisions between massive galaxies are just as important as those many small snacks."

The new study -- published recently in The Astrophysical Journal -- was conducted by Bolton's team from the Sloan Digital Sky Survey-III using the survey's 2.5-meter optical telescope at Apache Point, N.M., and the Earth-orbiting Hubble Space Telescope.

The telescopes were used to observe and analyze 79 "gravitational lenses," which are galaxies between Earth and more distant galaxies. A lens galaxy's gravity bends light from a more distant galaxy, creating a ring or partial ring of light around the lens galaxy.

The size of the ring was used to determine the mass of each lens galaxy, and the speed of stars was used to calculate the concentration of mass in each lens galaxy.

Bolton conducted the study with three other University of Utah astronomers -- postdoctoral researcher Joel Brownstein, graduate student Yiping Shu and undergraduate Ryan Arneson -- and with these members of the Sloan Digital Sky Survey: Christopher Kochanek, Ohio State University; David Schlegel, Lawrence Berkeley National Laboratory; Daniel Eisenstein, Harvard-Smithsonian Center for Astrophysics; David Wake, Yale University; Natalia Connolly, Hamilton College, Clinton, N.Y.; Claudia Maraston, University of Portsmouth, U.K.; and Benjamin Weaver, New York University.

Big Meals and Snacks for Massive Elliptical Galaxies

The new study deals with the biggest, most massive kind of galaxies, known as massive elliptical galaxies, which each contain about 100 billion stars. Counting unseen "dark matter," they contain the mass of 1 trillion stars like our sun.

"They are the end products of all the collisions and mergers of previous generations of galaxies," perhaps hundreds of collisions," Bolton says.

Despite recent evidence from other studies that massive elliptical galaxies grow by eating much smaller galaxies, Bolton's previous computer simulations showed that collisions between large galaxies are the only galaxy mergers that lead, over time, to increased mass density on the center of massive elliptical galaxies.

When a small galaxy merges with a larger one, the pattern is different. The smaller galaxy is ripped apart by gravity from the larger galaxy. Stars from the smaller galaxy remain near the outskirts -- not the center -- of the larger galaxy.

"But if you have two roughly comparable galaxies and they are on a collision course, each one penetrates more toward the center of the other, so more mass ends up in the center," Bolton says.

Other recent studies indicate stars are spread more widely within galaxies over time, supporting the idea that massive galaxies snack on much smaller ones.

"We're finding galaxies are getting more concentrated in their mass over time even though they are getting less concentrated in the light they emit," Bolton says.

He believes large galaxy collisions explain the growing mass concentration, while galaxies gobbling smaller galaxies explain more starlight away from galactic centers.

"Both processes are important to explain the overall picture," Bolton says. "The way the starlight evolves cannot be explained by the big collisions, so we really need both kinds of collisions, major and minor -- a few big ones and a lot of small ones."

The new study also suggests the collisions between large galaxies are "dry collisions" -- meaning the colliding galaxies lack large amounts of gas because most of the gas already has congealed to form stars -- and that the colliding galaxies hit each other "off axis" or with what Bolton calls "glancing blows" rather than head-on.

Sloan Meets Hubble: How the Study Was Conducted

The University of Utah joined the third phase of the Sloan Digital Sky Survey, known as SDSS-III, in 2008. It involves about 20 research institutions around the world. The project, which continues until 2014, is a major international effort to map the heavens as a way to search for giant planets in other solar systems, study the origin of galaxies and expansion of the universe, and probe the mysterious dark matter and dark energy that make up most of the universe.

Bolton says his new study was "almost gravy" that accompanied an SDSS-III project named BOSS, for Baryon Oscillation Spectrographic Survey. BOSS is measuring the history of the universe's expansion with unprecedented precision. That allows scientists to study the dark energy that accelerates expansion of the universe. The universe is believed to be made of only 4 percent regular matter, 24 percent unseen "dark matter" and 72 percent yet-unexplained dark energy.

During BOSS' study of galaxies, computer analysis of light spectra emitted by galaxies revealed dozens of gravitational lenses, which were discovered because the signatures of two different galaxies are lined up.

Bolton's new study involved 79 gravitational lenses observed by two surveys:

- The Sloan Survey and the Hubble Space Telescope collected images and emitted-light color spectra from relatively nearby, older galaxies -- including 57 gravitational lenses -- 1 billion to 3 billion years back into the cosmic past.

- Another survey identified 22 lenses among more distant, younger galaxies from 4 billion to 6 billion years in the past.

The rings of light around gravitational-lens galaxies are named "Einstein rings" because Albert Einstein predicted the effect, although he wasn't the first to do so.

"The more distant galaxy sends out diverging light rays, but those that pass near the closer galaxy get bent into converging light rays that appear to us as of a ring of light around the closer galaxy," says Bolton.

The greater the amount of matter in a lens galaxy, the bigger the ring. That seems counterintuitive, but the larger mass pulls with enough gravity to make the distant star's light bend so much that lines of light cross as seen by the observer, creating a bigger ring.

If there is more matter concentrated near the center of a galaxy, the faster stars will be seen moving toward or being slung away from the galactic center, Bolton says.

Alternative Theories

Bolton and colleagues acknowledge their observations might be explained by theories other than the idea that galaxies are getting denser in their centers over time:

- Gas that is collapsing to form stars can increase the concentration of mass in a galaxy. Bolton argues the stars in these galaxies are too old for that explanation to work.

- Gravity from the largest massive galaxies strips neighboring "satellite" galaxies of their outskirts, leaving more mass concentrated in the centers of the satellite galaxies. Bolton contends that process is not likely to produce the concentration of mass observed in the new study and explain how the extent of that central mass increases over time.

- The researchers merely detected the boundary in each galaxy between the star-dominated inner regions and the outer regions, which are dominated by unseen dark matter. Under this hypothesis, the appearance of growing galaxy mass concentration over time is due to a coincidence in researchers' measurement method, namely that they are measuring younger galaxies farther from their centers and measuring older galaxies closer to their centers, giving an illusion of growing mass concentration in galactic centers over time. Bolton says this measurement difference is too minor to explain the observed pattern of matter density within the lens galaxies.

Read More

Nobel Prize in Chemistry 2012: Smart Receptors On Cell Surfaces

Nobel Prize in Chemistry 2012: Smart Receptors On Cell Surfaces

  9:32:00 AM    Science Lover

---

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2012 to Robert J. Lefkowitz Howard Hughes Medical Institute and Duke University Medical Center and Brian K. Kobilka Stanford University School of Medicine "for studies of G-protein-coupled receptors."

The seven-transmembrane α-helix structure of a 
G-protein-coupled receptor. (Credit: By Bensaccount at 
en.wikipedia [Public domain], from Wikimedia Commons)

Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein-coupled receptors.

For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.

Lefkowitz started to use radioactivity in 1968 in order to trace cells' receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.

Today this family is referred to as G-protein-coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein-coupled receptors.

The studies by Lefkowitz and Kobilka are crucial for understanding how G-protein-coupled receptors function. Furthermore, in 2011, Kobilka achieved another break-through; he and his research team captured an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell. This image is a molecular masterpiece -- the result of decades of research.

Read More

Coursera makes top college courses free online

Coursera makes top college courses free online

  8:53:00 AM    Science Lover

---

Daphne Koller and Andrew Ng share a vision in which anyone, no matter how destitute, can expand their minds and prospects with lessons from the world's top universities.

Coursera co-founders Andrew Ng and Daphne Koller

That dream was joined this week by a dozen vaunted academic institutions including Duke University, the Ecole Polytechnique Federale de Lausanne (EPFL) in Switzerland and the University of Edinburgh in Scotland.

The schools will add online versions of classes to Coursera.org, a website launched by Stanford University professors Koller and Ng early this year with debut offerings from Princeton, Stanford and two other US universities.

"We have a vision where students everywhere around the world, regardless of country, family circumstances or financial circle have access to top quality education whether to expand their minds or learn valuable skills," Koller said.

"Where education becomes a right, not a privilege."

Academic institutions are increasingly turning to the Internet as an educational platform. A Khan Academy website created by Massachusetts Institute of Technology (MIT) graduate Salman Khan provides thousands of video lectures.

The nonprofit behind prestigious TED gatherings recently launched a TED-Ed channel at YouTube that teams accomplished teachers with talented animators to make videos that captivate while they educate.

In May, Harvard University and MIT announced that they were teaming up to expand their online education programs -- and invited other institutions to jump on board.

Called edX, the $60 million joint venture builds on MIT's existing MITx platform that enables video lesson segments, embedded quizzes, immediate feedback, online laboratories and student-paced learning.

"Universities have come to realize that online is not a fad," Koller said. "The question is not whether to engage in this area but how to do it."

Coursera classes are free, and completion certificates are issued that people can use to win jobs or improve careers.

"If a student takes a Stanford computer class and a Princeton business class, it shows they are motivated and have skills," Koller said. "We know it has helped employees get better jobs."

Coursera is distinguishing itself with essentially virtual versions of real classes.

"A lot of what is out there is basically video with, perhaps, some static content like lecture notes," Koller said.

"We are providing an actual course exchange were people register and there is weekly homework that is graded with feedback about how they are doing."

Coursera classes launched in February with most of the courses slated to begin in the coming months but it has already attracted students in 190 countries, according to Koller.

Coursera uses crowd-sourcing to translate material into various languages and hopes to connect with French-speaking populations around the world with EPFL classes.

Hoping to spread knowledge around the world, Coursera is a way to inspire faculty to try new methods of teaching and find ways that Internet Age tools can enhance on-campus courses, according to Duke provost Peter Lange.

"Our faculty is incredibly excited by the idea of trying it out and seeing if we can learn from it," Lange said.

"I love the idealism of it; the potential to reach people who might never get the chance to attend the university."

Duke designs its online courses to get students involved, complete with social networking tools for collaborating outside of classes.

"This is a great experiment in innovation and learning," Lange said.

As of Friday, Coursera boasted about 740,000 students and that number is expected to soar as word spreads and class offerings expand.

Coursera plans to keep classes free but perhaps one day make money for operations by charging for course completion certificates or matching employers with qualified workers.

"Current ethos in Silicon Valley is that if you build a website that people keep coming back to and is changing the lives of millions, you can eventually make money," Koller said.

"If and when we develop revenue, universities will share in it."

Paying the bills is not a worry at Coursera due to generous backing that includes a $3.7 million combined investment by the University of Pennsylvania and the California Institute of Technology, as well as funding from venture capital powerhouse Kleiner Perkins Caufield & Byers.

Read More

'Minority Report' software hits the real world

'Minority Report' software hits the real world

  8:00:00 AM    Science Lover

---

The software behind the film "Minority Report" -- where Tom Cruise speeds through video on a large screen using only hand gestures -- is making its way into the real world.

The interface developed by scientist John Underkoffler has been commercialized by the Los Angeles firm Oblong Industries as a way to sift through massive amounts of video and other data.

And yes, the software can be used by law enforcement and intelligence services. But no, it is not the "pre-crime" detection program illustrated in the 2002 Steven Spielberg sci-fi film.

Kwin Kramer, chief executive of Oblong, said the software can help in searching through "big data" for information. It can also create souped-up video-conference capabilities where participants share data from multiple devices like smartphones and tablets, integrated into a large video display.

"We think the future of computing is multiuser, multiscreen, multidevice," Kramer told AFP.

"This system helps with big workflow problems."

A key part of the system is the gesture interface, which the company calls the "g-speak" spatial operating environment.

That grew out of a project by Underkoffler -- then a scientist at the prestigious Massachusetts Institute of Technology -- for "Minority Report," before he became chief scientist at startup Oblong.

"We have demo versions of this kind of software which show exactly the 'Minority Report' user experience, allowing you to move back and forth in time, or to zoom in to look at details," Kramer said.

He said the same software can help businesses to "allow better collaboration, visualization and analysis of large amounts of data.

"You can have a lot of data but it's hard to make use of that," Kramer said.

"It can be on different machines and hard to access. This allows multiple people to look at that."

An employee demonstrates the use of a data glove to navigate a map on a computer screen at Los Angeles-based software company Oblong Industries' offices in Washington in June 2012. The software behind the film "Minority Report" -- where Tom Cruise speeds through video on a large screen using only hand gestures -- is making its way into the real world.

Gestural interfaces have been developed for other firms including Microsoft's Kinect but Oblong says it has far more sophisticated systems which can use Kinect and more.

Some highly sensitive systems use a data glove which can be more precise than ordinary hand movements.

Oblong has contracts with firms such as Boeing, General Electric and Saudi Aramco to help in analyzing large amounts of data. It is also developing a gestural interface for onboard computers with automaker Audi.

It has raised an unspecified amount of venture capital from investors including Foundry Group, Energy Technology Ventures and Morgan Stanley Alternative Investment Partners.

Brad Feld, managing director at Foundry Group, said Oblong offers "a path to fundamentally change the way we interact with computers."

Yet the question Oblong often gets is how users can get the "Minority Report" software.

David Schwartz, the company's vice president for sales, said "We get calls from people in the military who say, 'I want the 'Minority Report' interface."

He said the systems could be used for a realistic version of high-tech software interfaces on TV shows like "CSI."

"They would like to get it for free," he added.

What makes the real-life version of the software different from the one seen on film is that Oblong does not supply the analytics of the futuristic "pre-crime" division.

That does not prevent a company or law enforcement agency from using the software and adding its own analytics.

"We think law enforcement and intelligence are big data users and we think our technology is the leader," Kramer said.

He said Oblong currently has no government customers in the United States or abroad but offers itself as "a core technology provider."

Still, Oblong leverages its role in the movies to get in the door, even if the software is not quite the same.

"I think most people look at those 'Minority Report' interfaces and imagine how they could use that flexible system in their own office or designs studio," Kramer said.

"It isn't science fiction, it's real."

Read More

Entire Genetic Sequence of Individual Human Sperm Determined

Entire Genetic Sequence of Individual Human Sperm Determined

  11:46:00 AM    Science Lover

---

The entire genomes of 91 human sperm from one man have been sequenced by Stanford University researchers. The results provide a fascinating glimpse into naturally occurring genetic variation in one individual, and are the first to report the whole-genome sequence of a human gamete -- the only cells that become a child and through which parents pass on physical traits.

Every sperm cell looks essentially the same, with that characteristic tadpole appearance. But inside, sperm cells carry differences within their genes -- even cells from the same man. Now, researchers provide a detailed picture of how the cell's DNA varies in a new study published in the July 20, 2012 issue of the Cell Press journal Cell. The techniques used could be helpful for understanding male reproductive disorders or, when applied to other areas of research, for characterizing normal and diseased cells in the body. (Credit: iStockphoto/Alexandr Mitiuc)

"This represents the culmination of nearly a decade of work in my lab," said Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics. "We now have devices that will allow us to routinely amplify and sequence to a high degree of accuracy the entire genomes of single cells, which has far-ranging implications for the study of cancer, infertility and many other disorders."

Quake is the senior author of the research, published July 20 in Cell. Graduate student Jianbin Wang and former graduate student H. Christina Fan, PhD, now a senior scientist at ImmuMetrix, share first authorship of the paper.

Sequencing sperm cells is particularly interesting because of a natural process called recombination that ensures that a baby is a blend of DNA from all four of his or her grandparents. Until now, scientists had to rely on genetic studies of populations to estimate how frequently recombination had occurred in individual sperm and egg cells, and how much genetic mixing that entailed.

"Single-sperm sequencing will allow us to chart and understand how recombination differs between individuals at the finest scales. This is an important proof of principle that will allow us to study both fundamental dynamics of recombination in humans and whether it is involved in issues relating to male infertility," said Gilean McVean, PhD, professor of statistical genetics at the Wellcome Trust Centre for Human Genetics. McVean was not involved in the research.

The Stanford study showed that the previous, population-based estimates were, for the most part, surprisingly accurate: on average, the sperm in the sample had each undergone about 23 recombinations, or mixing events. However, individual sperm varied greatly in the degree of genetic mixing and in the number and severity of spontaneously arising genetic mutations. Two sperm were missing entire chromosomes. The study has long-ranging implication for infertility doctors and researchers.

"For the first time, we were able to generate an individual recombination map and mutation rate for each of several sperm from one person," said study co-author Barry Behr, PhD, HCLD, professor of obstetrics and gynecology and director of Stanford's in vitro fertilization laboratory. "Now we can look at a particular individual, make some calls about what they would likely contribute genetically to an embryo and perhaps even diagnose or detect potential problems."

Most cells in the human body have two copies of each of 23 chromosomes, and are known as "diploid" cells. Recombination occurs during a process called meiosis, which partitions a single copy of each chromosome into a sperm (in a man) or egg (in a woman) cell. When a sperm and an egg join, the resulting fertilized egg again has a full complement of DNA.

To ensure an orderly distribution during recombination, pairs of chromosomes are lined up in tight formation along the midsection of the cell. During this snug embrace, portions of matching chromosomes are sometimes randomly swapped. The process generates much more genetic variation in a potential offspring than would be possible if only intact chromosomes were segregated into the reproductive cells.

"The exact sites, frequency and degree of this genetic mixing process is unique for each sperm and egg cell," said Quake, "and we've never before been able to see it with this level of detail. It's very interesting that what happens in one person's body mirrors the population average."

Major problems with the recombination process can generate sperm missing portions or even whole chromosomes, making them incapable of or unlikely to fertilize an egg. But it can be difficult for fertility researchers to identify potential problems.

"Most of the techniques we currently use to assess sperm viability are fairly crude," said Quake.

To conduct the research, Wang, Quake and Behr first isolated and sequenced nearly 100 sperm cells from the study subject, a 40-year-old man. The man has healthy offspring, and the semen sample appeared normal. His whole-genome sequence (obtained from diploid cells) has been previously sequenced to a high level of accuracy.

They then compared the sequence of the sperm with that of the study subject's diploid genome. They could see, by comparing the sequences of the chromosomes in the diploid cells with those in the haploid sperm cells, where each recombination event took place. The researchers also identified 25 to 36 new single nucleotide mutations in each sperm cell that were not present in the subject's diploid genome. Such random mutations are another way to generate genetic variation, but if they occur at particular points in the genome they can have deleterious effects.

It's important to note that individual sperm cells are destroyed by the sequencing process, meaning that they couldn't go on to be used for fertilization. However, the single-cell sequencing described in the paper could potentially be used to diagnose male reproductive disorders and help infertile couples assess their options. It could also be used to learn more about how male fertility and sperm quality change with increasing age.

"This could serve as a new kind of early detection system for men who may have reproductive problems," said Behr, who also co-directs Stanford's reproductive endocrinology and infertility program. "It's also possible that we could one day use other, correlating features to harmlessly identify healthy sperm for use in IVF. In the end, the DNA is the raw material that ultimately defines a sperm's potential. If we can learn more about this process, we can better understand human fertility."

The research was supported by the National Institute of Health, the Chinese Scholarship Council and the Siebel Foundation.

Read More

A Wrinkle in Space-Time: Math Shows How Shockwaves Could Crinkle Space

A Wrinkle in Space-Time: Math Shows How Shockwaves Could Crinkle Space

  11:20:00 AM    Science Lover

---

Mathematicians at UC Davis have come up with a new way to crinkle up the fabric of space-time -- at least in theory.

Illustration of twisted space-time around Earth. (Credit: NASA)

"We show that space-time cannot be locally flat at a point where two shock waves collide," said Blake Temple, professor of mathematics at UC Davis. "This is a new kind of singularity in general relativity."

The results are reported in two papers by Temple with graduate students Moritz Reintjes and Zeke Vogler, respectively, both published in the journal Proceedings of the Royal Society A.

Einstein's theory of general relativity explains gravity as a curvature in space-time. But the theory starts from the assumption that any local patch of space-time looks flat, Temple said.

A singularity is a patch of space-time that cannot be made to look flat in any coordinate system, Temple said. One example of a singularity is inside a black hole, where the curvature of space becomes extreme.

Temple and his collaborators study the mathematics of how shockwaves in a perfect fluid can affect the curvature of space-time in general relativity. In earlier work, Temple and collaborator Joel Smoller, Lamberto Cesari professor of mathematics at the University of Michigan, produced a model for the biggest shockwave of all, created from the Big Bang when the universe burst into existence.

A shockwave creates an abrupt change, or discontinuity, in the pressure and density of a fluid, and this creates a jump in the curvature. But it has been known since the 1960s that the jump in curvature created by a single shock wave is not enough to rule out the locally flat nature of space-time.

Vogler's doctoral work used mathematics to simulate two shockwaves colliding, while Reintjes followed up with an analysis of the equations that describe what happens when shockwaves cross. He found this created a new type of singularity, which he dubbed a "regularity singularity."

What is surprising is that something as mild as interacting waves could create something as extreme as a space-time singularity, Temple said.

Temple and his colleagues are investigating whether the steep gradients in the space-time fabric at a regularity singularity could create any effects that are measurable in the real world. For example, they wonder whether they might produce gravity waves, Temple said. General relativity predicts that these are produced, for example, by the collision of massive objects like black holes, but they have not yet been observed in nature. Regularity singularities could also be formed within stars as shockwaves pass within them, the researchers theorize.

Reintjes, now a postdoctoral scholar at the University of Regensburg, Germany presented the work at the International Congress on Hyperbolic Problems in Padua, in June.

Read More

Visual Searches: Human Brain Beats Computers

Visual Searches: Human Brain Beats Computers

  8:48:00 PM    Science Lover

---

You're headed out the door and you realize you don't have your car keys. After a few minutes of rifling through pockets, checking the seat cushions and scanning the coffee table, you find the familiar key ring and off you go. Easy enough, right? What you might not know is that the task that took you a couple seconds to complete is a task that computers -- despite decades of advancement and intricate calculations -- still can't perform as efficiently as humans: the visual search.

Part of the research team in front of the Magnetic Resonance Imaging (MRI) device at the UCSB Brain Imaging Center From left to right : Researcher Tim Preston; Associate Professor of Psychological & Brain Sciences Barry Giesbrecht; and Professor of Psychological & Brain Sciences Miguel P. Eckstein. Not pictured: Koel Das, now a faculty member at the Indian Institute of Science in Bangalore, Karnatka, India; and lead author Fei Guo, now in the software industry. (Credit: Image courtesy of University of California - Santa Barbara)

"Our daily lives are composed of little searches that are constantly changing, depending on what we need to do," said Miguel Eckstein, UC Santa Barbara professor of psychological and brain sciences and co-author of the recently released paper "Feature-Independent Neural Coding of Target Detection during Search of Natural Scenes," published in the Journal of Neuroscience. "So the idea is, where does that take place in the brain?"

A large part of the human brain is dedicated to vision, with different parts involved in processing the many visual properties of the world. Some parts are stimulated by color, others by motion, yet others by shape.

However, those parts of the brain tell only a part of the story. What Eckstein and co-authors wanted to determine was how we decide whether the target object we are looking for is actually in the scene, how difficult the search is, and how we know we've found what we wanted.

They found their answers in the dorsal frontoparietal network, a region of the brain that roughly corresponds to the top of one's head, and is also associated with properties such as attention and eye movements. In the parts of the human brain used earlier in the processing stream, regions stimulated by specific features like color, motion, and direction are a major part of the search. However, in the dorsal frontoparietal network, activity is not confined to any specific features of the object.

"It's flexible," said Eckstein. Using 18 observers, an MRI machine, and hundreds of photos of scenes flashed before the observers with instructions to look for certain items, the scientists monitored their subjects' brain activity. By watching the intraparietal sulcus (IPS), located within the dorsal frontoparietal network, the researchers were able to note not only whether their subjects found the objects, but also how confident they were in their finds.

The IPS region would be stimulated even if the object was not there, said Eckstein, but the pattern of activity would not be the same as it would had the object actually existed in the scene. The pattern of activity was consistent, even though the 368 different objects the subjects searched for were defined by very different visual features. This, Eckstein said, indicates that IPS did not rely on the presence of any fixed feature to determine the presence or absence of various objects. Other visual regions did not show this consistent pattern of activity across objects.

"As you go further up in processing, the neurons are less interested in a specific feature, but they're more interested in whatever is behaviorally relevant to you at the moment," said Eckstein. Thus, a search for an apple, for instance, would make red, green, and rounded shapes relevant. If the search was for your car keys, the interparietal sulcus would now be interested in gold, silver, and key-type shapes and not interested in green, red, and rounded shapes.

"For visual search to be efficient, we want those visual features related to what we are looking for to elicit strong responses in our brain and not others that are not related to our search, and are distracting," Eckstein added. "Our results suggest that this is what is achieved in the intraparietal sulcus, and allows for efficient visual search."

For Eckstein and colleagues, these findings are just the tip of the iceberg. Future research will dig more deeply into the seemingly simple yet essential ability of humans to do a visual search and how they can use the layout of a scene to guide their search.

"What we're trying to really understand is what other mechanisms or strategies the brain has to make searches efficient and easy," said Eckstein. "What part of the brain is doing that?"

Research on this study was also conducted by Tim Preston, Koel Das, Barry Giesbrecht, and first author Fei Guo, all from UC Santa Barbara.

Read More

Diabetes Drug Makes Brain Cells Grow

Diabetes Drug Makes Brain Cells Grow

  2:00:00 PM    Science Lover

---

The widely used diabetes drug metformin comes with a rather unexpected and alluring side effect: it encourages the growth of new neurons in the brain. The study reported in the July 6th issue of Cell Stem Cell, a Cell Press publication, also finds that those neural effects of the drug also make mice smarter.

New research finds that the widely used diabetes drug 
metformin comes with a rather unexpected and alluring 
side effect: it encourages the growth of new neurons in 
the brain. (Credit: iStockphoto/Guido Vrola)

The discovery is an important step toward therapies that aim to repair the brain not by introducing new stem cells but rather by spurring those that are already present into action, says the study's lead author Freda Miller of the University of Toronto-affiliated Hospital for Sick Children. The fact that it's a drug that is so widely used and so safe makes the news all that much better.

Earlier work by Miller's team highlighted a pathway known as aPKC-CBP for its essential role in telling neural stem cells where and when to differentiate into mature neurons. As it happened, others had found before them that the same pathway is important for the metabolic effects of the drug metformin, but in liver cells.

"We put two and two together," Miller says. If metformin activates the CBP pathway in the liver, they thought, maybe it could also do that in neural stem cells of the brain to encourage brain repair.

The new evidence lends support to that promising idea in both mouse brains and human cells. Mice taking metformin not only showed an increase in the birth of new neurons, but they were also better able to learn the location of a hidden platform in a standard maze test of spatial learning.

While it remains to be seen whether the very popular diabetes drug might already be serving as a brain booster for those who are now taking it, there are already some early hints that it may have cognitive benefits for people with Alzheimer's disease. It had been thought those improvements were the result of better diabetes control, Miller says, but it now appears that metformin may improve Alzheimer's symptoms by enhancing brain repair.

Miller says they now hope to test whether metformin might help repair the brains of those who have suffered brain injury due to trauma or radiation therapies for cancer.

Read More