Meet the Nimble-Fingered Interface of the Future

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Low-cost microscope uses holograms, not lenses

Researchers at UCLA have built a compact, light-weight, dual-mode microscope that uses holograms instead of lenses, and which they say is ideal for use in developing countries. The prototype fits in the palm of a hand, and has a materials cost of under $100.

It has two modes: a transmission mode that can probe relatively large volumes of blood or water, and a reflection mode that can image denser, opaque samples. The spatial resolution for both modes is less than two micrometers — comparable to that achieved by far bulkier microscopes with low- to medium-power lenses.

"This is the first demonstration of essentially a hand-held version of a microscope that can do dual-mode imaging within a very compact and cost-effective form," says associate professor of electrical engineering and bioengineering Aydogan Ozcan.

The microscope could help ensure water quality, test patients' blood for harmful bacteria, and also prove useful in health crises such as the recent outbreak of E coli in Europe.

"It's a very challenging task to detect E. coli in low concentrations in water and food," Ozcan says. "This microscope could be part of a solution for field investigation of water, or food, or maybe pathogens in blood."
Instead of lenses, this microscope uses holograms. An inexpensive light source is divided into two beams — one that interacts with microscopic cells or particles in the sample, and another that does not. The beams then pass to an adjacent sensor chip, where their interference pattern is recorded.

Software analyzes that pattern and recreates the path taken by the light. The raw data is then processed on a laptop to reconstruct the images.
Ozcan says he has founded a company aimed at commercializing the device.

By Kate Taylor 
From tgdaily

Up from the Depths: How Bacteria Capture Carbon in the 'Twilight Zone'

Details are now emerging about a microbial metabolic pathway that helps solve the mystery of how certain bacteria do this in the dark ocean. These research results, which are enabling a better understanding of what happens to the carbon that is fixed in the oceans every year, were published by a team of researchers, including those from the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), in the Sept. 2, 2011 edition of Science.

 Bigelow’s Dashiell Masland working with a Tecan Freedom EVO robotic liquid handler.

Carbon fixation in the dark ocean has so far been attributed primarily to the Archaea, single-celled organisms that often live in extreme environmental conditions. In this region of the ocean, the bacteria living there were thought to rely on organic compounds for both energy and carbon. According to DOE JGI collaborator Ramunas Stepanauskas, Director of the Bigelow Laboratory Single Cell Genomics Center and senior author of the Science paper, "Previous oceanographic models suggested that Archaea do not adequately account for the amount of carbon that is being fixed in the dark ocean. Our study discovered specific types of Bacteria rather than Archaea, and their likely energy sources that may be responsible for this major, unaccounted component of the dark ocean carbon cycle."

To overcome the challenge that had hindered studies of deep ocean microbes, which have not yet been cultivated in the laboratory, researchers employed innovative single-cell genomics techniques, where DOE JGI's Tanja Woyke and Alexander Sczyrba, Bigelow Laboratory's Ramunas Stepanauskas and their teams are among the pioneers. Study co-author Woyke explained, "After we sequenced the genomes of single cells that were isolated by our colleagues at Bigelow, it was possible to verify the predominant bacterial lineages capable of trapping carbon in this deep underwater region. "This study represents a pristine example for the use of single cell genome sequencing to decipher the metabolic capabilities of uncultured natural microbial consortia, providing a powerful complement to metagenomics."

Stepanauskas attributed the success of the project to the combined efforts of the DOE JGI, the Bigelow Laboratory, the Monterey Bay Aquarium Research Institute, the University of Vienna, and MIT. "This is the first application of a single-cell genomic approach to the deep ocean, one of the largest and least known biomes on the planet," emphasized David Kirchman, Harrington Professor of Marine Biosciences at the University of Delaware. "The paper radically changes our view about how microbes gain energy and flourish in the oceans.

From sciencedaily

Artificial light-harvesting method achieves 100% energy transfer efficiency

The researchers, led by Shinsuke Takagi from the Tokyo Metropolitan University and PRESTO of the Japan Science and Technology Agency, have published their study on their work toward an artificial LHS in a recent issue of the Journal of the American Chemical Society.

 By arranging porphyrin dye molecules on a clay surface using the “Size-Matching Effect,” researchers have demonstrated an energy transfer efficiency of approximately 100%, which is an important requirement for designing efficient artificial light-harvesting systems.

“In order to realize an artificial light-harvesting system, almost 100% efficiency is necessary,” Takagi told “Since light-harvesting systems consist of many steps of energy transfer, the total energy transfer efficiency becomes low if the energy transfer efficiency of each step is 90%. For example, if there are five energy transfer steps, the total energy transfer is 0.9 x 0.9 x 0.9 x 0.9 x 0.9 = 0.59. In this way, an efficient energy transfer reaction plays an important role in realizing efficient sunlight collection for an artificial light-harvesting system.”

As the researchers explain in their study, a natural LHS (like those in purple bacteria or plant leaves) is composed of regularly arranged molecules that efficiently collect sunlight and carry the excitation energy to the system’s reaction center. An artificial LHS (or “artificial leaf”) attempts to do the same thing by using functional dye molecules. 

Building on the results of previous research, the scientists chose to use two types of porphyrin dye molecules for this purpose, which they arranged on a clay surface. The molecules’ tendency to aggregate or segregate on the clay surface made it challenging for the researchers to arrange the molecules in a regular pattern like their natural counterparts. 

“A molecular arrangement with an appropriate intermolecular distance is important to achieve nearly 100% energy transfer efficiency,” Takagi said. “If the intermolecular distance is too near, other reactions such as electron transfer and/or photochemical reactions would occur. If the intermolecular distance is too far, deactivation of excited dye surpasses the energy transfer reaction.” 

In order to achieve the appropriate intermolecular distance, the scientists developed a novel preparation technique based on matching the distances between the charged sites in the porphyrin molecules and the distances between negatively charged (anionic) sites on the clay surface. This effect, which the researchers call the “Size-Matching Rule,” helped to suppress the major factors that contributed to the porphyrin molecules’ tendency to aggregate or segregate, and fixed the molecules in an appropriate uniform intermolecular distance. As Takagi explained, this strategy is significantly different than other attempts at achieving molecular patterns.

“The methodology is unique,” he said. “In the case of usual self-assembly systems, the arrangement is realized by guest-guest interactions. In our system, host-guest interactions play a crucial role for realizing the special arrangement of dyes. Thus, by changing the host material, it is possible to control the molecular arrangement of dyes on the clay surface.”

As the researchers demonstrated, the regular arrangement of the molecules leads to an excited energy transfer efficiency of up to 100%. The results indicate that porphyrin dye molecules and clay host materials look like promising candidates for an artificial LHS.

“At the present, our system includes only two dyes,” Takagi said. “As the next step, the combination of several dyes to adsorb all sunlight is necessary. One of the characteristic points of our system is that it is easy to use several dyes at once. Thus, our system is a promising candidate for a real light-harvesting system that can use all sunlight. We believe that even photochemical reaction parts can be combined on the same clay surface. If this system is realized and is combined with a photochemical reaction center, this system can be called an ‘inorganic leaf.’”

By Lisa Zyga
From physorg

Heat from Fingertips Could Help ATM Hackers

The secret codes typed in by banking customers can be recorded using the residual heat left behind on the keypad, says a group of researchers from the University of California at San Diego.

The group's paper, presented earlier this month at the USENIX Workshop on Offensive Technologies, shows that a digital infrared camera can read the digits of a customer's PIN number on the keypad more than 80 percent of the time if used immediately. And if the camera is used a minute later, says Keaton Mowery, a doctoral student in computer science at UCSD, it can still detect the correct digits about half the time.

 Hot hacker: A typical ATM keypad is shown at top. Below is a thermal image taken immediately after it's been used. The code in this case was 1485.

The research, which Mowery conducted with fellow student Sarah Meiklejohn and professor Stefan Savage, is based on previous work by well-known security researcher Michal Zalewski, who in 2005 used an infrared camera to detect codes punched into a safe with a keypad lock. While Zalewski was able to detect the codes even after five minutes, the UCSD researchers found that the chance of extracting the proper digits dropped to about 20 percent after 90 seconds.

The infrared method can circumvent defensive strategies, such as shielding the keypad. However, an ATM user could evade this infrared surveillance merely by placing a hand over the entire keypad to warm all of the keys, says Mowery. And if an ATM also uses the keypads for entering other numbers, such as the amount of money to withdraw, it contributes additional noise, says Meiklejohn.

The method has other weaknesses as well. "With plastic keypads, we can reliably detect which buttons were pressed, but it is really difficult to determine the order," Mowery says. Even if the image was recorded immediately after the user typed it in, the order of the digits was only detectable about 20 percent of the time. 

And if the keypad is metal, fuhgeddaboudit. "Essentially, if you pointed the camera directly at the metal keypad, it would show you the thermal fingerprint of you, the camera operator, rather than of the keypad itself," Meiklejohn says. "However, we didn't push it, because the plastic keypad did work. It's possible that someone else could solve those issues."

Combine all of these shortcomings with the cost of the infrared camera—$2,000 a month to rent, about $18,000 to buy—and the likelihood of anyone attacking an ATM this way is low, says researcher Zalewski. "Miniature daylight cameras are a lot simpler and more reliable," he says. 

By Robert Lemos
From Technology Review

Quantum Processor Hooks Up with Quantum Memory

Researchers at the University of California, Santa Barbara, have become the first to combine a quantum processor with memory that can be used to store instructions and data. This achievement in quantum computing replicates a similar milestone in conventional computer design from the 1940s.

 Super cool: When chilled almost to absolute zero, this chip becomes a quantum computer that includes both a processor (the two black squares) and memory (the snaking lines on either side).

Although quantum computing is now mostly a research subject, it holds out the promise of computers far more capable than those we use today. The power of quantum computers comes from their version of the most basic unit of computing, the bit. In a conventional computer, a bit can represent either 1 or 0 at any time. Thanks to the quirks of quantum mechanics, the equivalent in a quantum computer, a qubit, can represent both values at once. When qubits in such a "superposition" state work together, they can operate on exponentially more data than the same number of regular bits. As a result, quantum computers should be able to defeat encryption that is unbreakable in practice today and perform highly complex simulations.

Linking a processor and memory elements brings such applications closer, because it should make it more practical to control and program a quantum computer can perform, says Matteo Mariantoni, who led the project, which is part of a wider program at UCSB headed by John Martinis and Andrew Cleland.

The design the researchers adopted is known as the von Neumann architecture—named after John von Neumann, who pioneered the idea of making computers that combine processor and memory. Before the first von Neumann designs were built in the late 1940s, computers could be reprogrammed only by physically reconfiguring them. "Every single computer we use in our everyday lives is based on the von Neumann architecture, and we have created the quantum mechanical equivalent," says Mariantoni.
The only quantum computing system available to buy—priced at $10 million—lacks memory and works like a pre-von Neumann computer.

Qubits can be made in a variety of ways, such as suspending ions or atoms in magnetic fields. The UCSB group used more conventional electrical circuits, albeit ones that must be cooled almost to absolute zero to make them superconducting and activate their quantum behavior.  They can be fabricated by chip-making techniques used for conventional computers. Mariantoni says that using superconducting circuits allowed the team to place the qubits and memory elements close together on a single chip, which made possible the new von Neumann-inspired design.

The processor consists of two qubits linked by a quantum bus that enables them to communicate. Each is also connected to a memory element into which the qubit can save its current value for later use, serving the function of the RAM - for random access memory - of a conventional computer. The links between the qubits and the memory contain devices known as resonators, zigzagging circuits inside which a qubit's value can live on for a short time.

Mariantoni's group has used the new system to run an algorithm that is a kind of computational building block, called a Toffoli gate, which can be used to implement any conventional computer program. The team also used its design to perform a mathematical operation that underlies to the algorithm with which a quantum computer might crack complex data encryption.

David Schuster leads a group at the University of Chicago that also works on quantum computing, including superconducting circuits. He says that superconducting circuits have recently proved to be comparatively reliable. "One of the next big frontiers for these techniques now is scale," he says. By replicating the Von Neumann architecture the UCSB team have expanded that frontier.

That's not to say that quantum computers must all adopt that design, though, as conventional computers have. "You could make a computer completely out of qubits and it could do every kind of calculation," says Schuster. However there are advantages to making use of resonators like those that make up the new design's memory, he says. "Resonators are easier and more reliable to make than qubits and easier to control," says Schuster.

Mariantoni agrees. "We can easily scale the number of these unit cells," he says. "I believe that arrays of resonators will represent the future of quantum computing with integrated circuits."

By Tom Simonite
From Technology Review

An RNA Switch for Stem Cells

RNA molecules have long been known for their role in translating genes to proteins inside a cell, but more recently, scientists have found large numbers of RNA molecules that don't code for proteins but seem to have other cellular roles. Most research in mammals has focused on tiny RNA molecules called microRNAs, but a new study, published this week in Nature, describes the far-reaching effects of much larger and relatively unstudied RNA molecules called lincRNAs (short for large intergenic noncoding RNAs). The study identifies lincRNAs that play a role in the function of embryonic stem cells, and suggests trying to use lincRNAs to manipulate these cells to spawn other cell types.

 Missing link: Large RNA molecules called lincRNAs turn out to have an important role in controlling the function and fate of embryonic stem cells, like those pictured here.

Mitchell Guttman, first author of the study and a graduate student at MIT and the Broad Institute, says that when the Broad team discovered more than 3,500 unique lincRNAs in the human and mouse genomes in 2009, "the potential was enormous, and we wanted to know what they could be doing."

To answer that question, the researchers focused on understanding lincRNAs' role in embryonic stem cells. Using a technique called RNA interference, they systematically shut down the function of each of more than 200 lincRNAs previously identified as playing a role in embryonic stem cells. They then profiled the genes expressed in the cells and studied their functions. They found that most lincRNAs have widespread effects on cells, and that they help control the fate of stem cells. The team identified about two dozen lincRNAs that help maintain the cell's pluripotency—its ability to beget all other kinds of cells—and a similar number of lincRNAs that repress genes involved in differentiating into other cell types. 

Nudging stem cells to differentiate has proved challenging so far, and scientists have been looking for better ways. Guttman says that inhibiting lincRNAs in specific combinations may make it possible to direct stem cells to transform in specific ways. George Daley, a stem-cell biologist at Harvard Medical School and Children's Hospital Boston, says that further probing the effects of lincRNAs "will help refine our capacity to control and manipulate cells in culture, and this will advance the utility of stem cells for regenerative medicine."

Tariq Rana, an RNA biologist at Sanford-Burnham Medical Research Institute in La Jolla, California, calls the work "the first comprehensive study defining the functional roles of lincRNAs in embryonic stem cells." He says it will launch new investigations into how lincRNAs regulate gene expression. 

Guttman and colleagues propose that lincRNAs have an important coordinating function in the cell: like sergeants commanding military units, single lincRNAs seem to interact with and control large complexes of proteins. He says that these large RNAs also seem to be put together in a modular way, like molecular Tinkertoys. Learning how they're put together could allow scientists to design and assemble RNAs to perform very specific tasks—and manipulate cells. 

By Courtney Humphries
From Technology Review

Old Blood Impairs Young Brains

It's a cliché of vampire tales that young blood is preferable to old, but a new study suggests there's some truth to it. 

A paper published today in Nature finds that when younger mice are exposed to the blood of older mice, their brain cells behave more like those found in aging brains, and vice versa. The researchers who carried out the work also uncovered chemical signals in aged blood that can dampen the growth of new brain cells, suggesting that the decline in brain function with age could be caused in part by blood-borne factors rather than an intrinsic failure of brain cells. 

 Brain boost: Normally the brains of older mice (left) grow fewer new neurons (dark brown) than when the animals were younger. But when older mice shared the blood of younger mice, their neurons grew more robustly (right).

To arrive at the discovery, the researchers studied pairs of old and young mice that were literally joined at the hip. They used a technique called parabiosis, in which two mice are surgically joined together along the flank, which causes them to develop a shared circulatory system. The technique has been used to study the development of the blood system, and more recently has been used to investigate the effects of age by joining old and young mice. 

Lead author Tony Wyss-Coray, a neuroscientist at Stanford University, says that five weeks after creating these May-December pairings, "we found striking effects both on the young and old brains." The young mice had a reduction in the production of new neurons (neurogenesis), an increase in brain inflammation, and less activity in synapses connecting neurons.

The older mice, in contrast, had an increase in new neurons, less inflammation, and greater activity at synapses. "You could almost call this a rejuvenation effect," Wyss-Coray says.

To see whether the effect could influence behavior, they injected, in separate experiments, young mice with plasma from older mice and vice versa, and found that old plasma impaired the younger animals' ability to perform learning and memory tasks, whereas young plasma improved the abilities of older mice.

Blood cells from one mouse cannot travel into the brain of the other because of the blood-brain barrier, so the team concluded that free-floating molecules in the blood, capable of passing through, must be responsible for the effects. By comparing more than 60 chemokines—chemical messengers secreted by cells that circulate in the blood—the researchers identified several associated with the detrimental effect of old blood. Administering one of these chemicals, called CCL11, to young mice dampened neurogenesis and impaired learning and memory. CCL11 has been studied for its role in allergies and asthma, but it's not clear how it influences neurons.

Richard Ransohoff, director of the Neuroinflammation Research Center at the Cleveland Clinic, who was not involved with the work, says that the work is intriguing in the context of a study that last year linked neurogenesis to the ratio of two different types of immune cells in the blood. Both findings are "very, very surprising," he says, and suggest that "the process of neurogenesis can be affected from outside the brain." Because stem cells that give rise to new neurons "live in a microenvironment, and that environment is very intimately associated with blood vessels," he says, these cells may be influenced by chemicals that travel through the blood, including signals from the immune system.

Wyss-Coray says that the group will continue investigating whether specific blood factors cause cognitive decline with age—or offer protective effects in younger brains. Ransohoff also points out that such factors could be useful as biomarkers for neurogenesis and other signs of brain health, since the blood is vastly more accessible than the brain.

By Courtney Humphries
From Technology Review