Tuesday, December 31, 2013

The age of artificial intelligence is here.  At http://www.examiner.com/article/the-age-of-artificial-intelligence-is-here

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Tech predictions for businesses in 2014: mobility, wearables, intelligent assistants, gestural computing, facial recognition. At http://www.kurzweilai.net/tech-predictions-for-businesses-in-2014-mobility-wearables-intelligent-assistants-gestural-computing-facial-recognition

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A step toward simulating a worm brain in a computer. At http://www.kurzweilai.net/a-step-toward-simulating-a-worm-brain-in-a-computer

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World’s first green piglets born in China, sheep next. At http://www.kurzweilai.net/worlds-first-green-piglets-born-in-china-sheep-next

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First human implant of world’s smallest, minimally invasive cardiac pacemaker. At http://www.kurzweilai.net/first-human-implant-of-worlds-smallest-minimally-invasive-cardiac-pacemaker

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RIKEN to develop exascale supercomputer by 2020. At http://www.kurzweilai.net/riken-to-develop-exascale-supercomputer-by-2020

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The best neuroscience images of 2013. At http://www.kurzweilai.net/the-best-neuroscience-images-of-2013

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Friday, December 27, 2013

How we process numbers is revealed in our brain structure

December 24, 2013
Relative changes in gray-matter volume (credit: Donders Institute, University of Nijmegen)
How to you visualize numbers? Spatially, or in some other way?
For a long time, scientists thought that everyone processed numbers predominantly in a spatial way (low to high numbers visualized as left to right).
More recently, several studies have shown associations between numbers and non-spatial representations of magnitude, such as physical size,  grip opening, object graspability, tactile sensation, force (against a button, for example), and luminosity.
Gray-matter volume differences
A study by Florian Krause from the Donders Institute in Radboud University Nijmegen in the Netherlands,  just published in the Journal of Cognitive Neuroscience, has now found that these individual differences are related to specific brain structures.
In MRI scans of test subjects, he discovered differences in gray-matter volume in two specific locations:
  • Spatially oriented brains have an above-average grey matter volume in the right precuneus, a small area of the brain associated with processing visual-spatial information.
  • Non-spatially oriented brains have more grey matter in the left angular gyrus, an area associated with semantic and conceptual processing.
The thirty people taking part in the study were put into an MRI scanner and were shown numbers between 1 and 9 (except 5). In two consecutive judgement tasks, they had to classify the presented digits as odd or even. Both tasks differed only in the required response: in the spatial task, subjects had to click with their index finger or middle finger to classify the digits (that is left or right position), and in the non-spatial task they applied either a small or a large force on a pressure sensor with their thumb.
Importantly, participants coupled the spatial response as well as the force response to the size of the presented number, as they responded faster with a left or soft press for small numbers and with a right or hard press for large numbers. Krause worked out those couplings for each subject, and compared the scores with the information from their brain scan.
At present, math is largely taught on the basis of a spatial number processing. “People with a non-spatial representation of numbers would probably benefit from a different approach to maths teaching,” says Krause. “It is possible to let pupils experience the size of numbers in a non-spatial way. This could involve expressing numbers with your body while doing simple arithmetics, for example.” Krause is planning several new studies to explore the scientific basis of methods like these in more detail.
So how does this relate to reports of how Einstein, Feynman, and others used kinesthetic imaging, music, sounds, and other methods to represent physics principles?

Abstract of Journal of Cognitive Neuroscience paper
A dominant hypothesis on how the brain processes numerical size proposes a spatial representation of numbers as positions on a “mental number line.” An alternative hypothesis considers numbers as elements of a generalized representation of sensorimotor-related magnitude, which is not obligatorily spatial. Here we show that individuals’ relative use of spatial and nonspatial representations has a cerebral counterpart in the structural organization of the posterior parietal cortex. Interindividual variability in the linkage between numbers and spatial responses (faster left responses to low numbers and right responses to high numbers; spatial–numerical association of response code effect) correlated with variations in gray matter volume around the right precuneus. Conversely, differences in the disposition to link numbers to force production (faster soft responses to low numbers and hard responses to high numbers) were related to gray matter volume in the left angular gyrus. This finding suggests that numerical cognition relies on multiple mental representations of analogue magnitude using different neural implementations that are linked to individual traits.

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The brain’s visual data-compression algorithm

December 24, 2013
Data compression in the brain: When the primary visual cortex processes sequences of complete images and images with missing elements — here vertical contours — it “subtracts” the images from each other (the brain computes the differences between the images). Under certain circumstances, the neurons forward these image differences (bottom) rather than the entire image information (upper left). (Credit: RUB, Jancke)
Researchers have assumed that visual information in the brain was transmitted almost in its entirety from its entry point, the primary visual cortex (V1).
“We intuitively assume that our visual system generates a continuous stream of images, just like a video camera,” said Dr. Dirk Jancke from the Institute for Neural Computation at Ruhr University.
“However, we have now demonstrated that the visual cortex suppresses redundant information and saves energy by frequently forwarding image differences,” similar to methods used for video data compression in communication technology. The study was published in Cerebral Cortex (open access).
Using recordings in cat visual cortex, Jancke and associates recorded the neurons’ responses to natural image sequences such as vegetation, landscapes, and buildings. They created two versions of the images: a complete one, and one in which they had systematically removed vertical or horizontal contours.
If these individual images were presented at 33Hz (30 milliseconds per image), the neurons represented complete image information. But at 10Hz (100 milliseconds), the neurons represented only those elements that were new or missing, that is, image differences.
To monitor the dynamics of neuronal activities in the brain in the millisecond range, the scientists used voltage-dependent dyes. Those substances fluoresce when neurons receive electrical impulses and become active, measured across a surface of several square millimeters. The result is a temporally and spatially precise record of transmission processes within the neuronal network.

Abstract of Cerebral Cortex paper
The visual system is confronted with rapidly changing stimuli in everyday life. It is not well understood how information in such a stream of input is updated within the brain. We performed voltage-sensitive dye imaging across the primary visual cortex (V1) to capture responses to sequences of natural scene contours. We presented vertically and horizontally filtered natural images, and their superpositions, at 10 or 33 Hz. At low frequency, the encoding was found to represent not the currently presented images, but differences in orientation between consecutive images. This was in sharp contrast to more rapid sequences for which we found an ongoing representation of current input, consistent with earlier studies. Our finding that for slower image sequences, V1 does no longer report actual features but represents their relative difference in time counteracts the view that the first cortical processing stage must always transfer complete information. Instead, we show its capacities for change detection with a new emphasis on the role of automatic computation evolving in the 100-ms range, inevitably affecting information transmission further downstream.

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DNA motor ‘walks’ along nanotube, transports nanoparticle cargo

December 24, 2013
This illustration depicts the walking mechanism of a new type of DNA motor that researchers have demonstrated by using it to transport a nanoparticle along the length of a carbon nanotube. The core is made of an enzyme that cleaves off part of a strand of RNA. After cleavage, the upper DNA arm moves forward, binding with the next strand of RNA, and then the rest of the DNA follows. (Credit: Purdue University image/Tae-Gon Cha)
Researchers have created a new type of molecular motor made of DNA and demonstrated its potential by using it to transport a nanoparticle along the length of a carbon nanotube.
The design was inspired by natural biological motors that have evolved to perform specific tasks critical to the function of cells, said Jong Hyun Choi, a Purdue University assistant professor of mechanical engineering.
Controllable synthetic motors
Biological motors are made of protein, which cannot be controlled, and they don’t function outside their natural environment.  So researchers are trying to create synthetic motors based on DNA. The walking mechanism of these DNA motors is far slower than the mobility of natural motors, but DNA-based motors are more stable and might be switched on and off, Choi said.
Molecular model of a nanoparticle-functionalized, DNAzyme-based motor on an RNA-decorated (blue) nanotube track. The DNAzyme motor consists of a catalytic core (green) and recognition arms (red). Cadmium sulfide nanocrystals (yellow) and carbon nanotubes (black) are used as a model system for the cargo and a one-dimensional track. (Credit: Purdue University image/Tae-Gon Cha)
The new motor has a core and two arms made of DNA, one above and one below the core. As it moves along a carbon-nanotube track it continuously harvests energy from strands of RNA, molecules vital to a variety of roles in living cells and viruses.
“Our motors extract chemical energy from RNA molecules decorated on the nanotubes and use that energy to fuel autonomous walking along the carbon nanotube track,” Choi said.
The core is made of an enzyme that cleaves off part of a strand of RNA. After cleavage, the upper DNA arm moves forward, binding with the next strand of RNA, and then the rest of the DNA follows.
The process repeats until reaching the end of the nanotube track. Researchers used the motor to move nanoparticles of cadmium disulfide along the length of a nanotube. The nanoparticle is about 4 nanometers in diameter.
The motor took about 20 hours to reach the end of the nanotube, which was several microns long, but the process might be sped up by changing temperature and pH, a measure of acidity.
In coming decades, such molecular motors might find uses in drug delivery, manufacturing and chemical processing.
The new findings were detailed in a research paper published in the journal Nature Nanotechnology. The work has been supported by the U.S. Office of Naval Research.

Abstract of Nature Nanotechnology paper
Intracellular protein motors have evolved to perform specific tasks critical to the function of cells such as intracellular trafficking and cell division. Kinesin and dynein motors, for example, transport cargos in living cells by walking along microtubules powered by adenosine triphosphate hydrolysis. These motors can make discrete 8 nm centre-of-mass steps and can travel over 1 micrometer by changing their conformations during the course of adenosine triphosphate binding, hydrolysis and product release. Inspired by such biological machines, synthetic analogues have been developed including self-assembled DNA walkers that can make stepwise movements on RNA/DNA substrates or can function as programmable assembly lines. Here, we show that motors based on RNA-cleaving DNA enzymes can transport nanoparticle cargoes (CdS nanocrystals in this case) along single-walled carbon nanotubes. Our motors extract chemical energy from RNA molecules decorated on the nanotubes and use that energy to fuel autonomous, processive walking through a series of conformational changes along the one-dimensional track. The walking is controllable and adapts to changes in the local environment, which allows us to remotely direct GO and STOP actions. The translocation of individual motors can be visualized in real time using the visible fluorescence of the cargo nanoparticle and the near-infrared emission of the carbon-nanotube track. We observed unidirectional movements of the molecular motors over 3 micrometers with a translocation velocity on the order of 1 nm per min under our experimental conditions.

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Liquid crystal ‘flowers’ that can be used as lenses

December 24, 2013
bright field liquid crystal flower
A liquid crystal “flower” under magnification. The black dot at center is the silica bead that generates the flower’s pattern. (Credit: University of Pennsylvania)
A team of material scientists, chemical engineers and physicists from the University of Pennsylvania has made another advance in their effort to use liquid crystals as a medium for assembling structures.
In their earlier studies, the team produced patterns of “defects,” useful disruptions in the repeating patterns found in liquid crystals, in nanoscale grids and rings. The new study adds a more complex pattern out of an even simpler template: a three-dimensional array in the shape of a flower.
And because the petals of this “flower” are made of transparent liquid crystal and radiate out in a circle from a central point, the ensemble resembles a compound eye and can thus be used as a lens.
Directed assembly
The researchers’ ongoing work with liquid crystals is an example of a growing field of nanotechnology known as “directed assembly,” in which scientists and engineers aim to manufacture structures on the smallest scales without having to individually manipulate each component. Rather, they set out precisely defined starting conditions and let the physics and chemistry that govern those components do the rest.
The starting conditions in the researchers previous experiments were templates consisting of tiny posts. In one of their studies, they showed that changing the size, shape or spacing of these posts would result in corresponding changes in the patterns of defects on the surface of the liquid crystal resting on top of them. In another experiment, they showed they could make a “hula hoop” of defects around individual posts, which would then act as a second template for a ring of defects at the surface.
Kamien: planting a liquid-crystal seed of a compound eye (credit: University of Pennsylvania)
Crystal vision
In their latest work, the researchers used a much simpler cue. “Before we were growing these liquid crystals on something like a trellis, a template with precisely ordered features,” said Randall Kamien, professor in the School of Arts and Sciences’ Department of Physics and Astronomy. “Here, we’re just planting a seed.”
The seed, in this case, were silica beads — essentially, polished grains of sand. Planted at the top of a pool of liquid crystal flower-like patterns of defects grow around each bead.
In their experiment that generated grid patterns of defects, those patterns stemmed from cues generated by the templates’ microposts. Domains of elastic energy originated on the flat tops and edges of these posts and traveled up the liquid crystal’s layers, culminating in defects. Using a bead instead of a post, as the researchers did in their latest experiment, makes it so that the interface is no longer flat.
“Not only is the interface at an angle, it’s an angle that keeps changing,” Kamien said. “The way the liquid crystal responds to that is that it makes these petal-like shapes at smaller and smaller sizes, trying to match the angle of the bead until everything is flat.”
Surface tension on the bead also makes it so these petals are arranged in a tiered, convex fashion. And because the liquid crystal can interact with light, the entire assembly can function as a lens, focusing light to a point underneath the bead.
“It’s like an insect’s compound eye, or the mirrors on the biggest telescopes,” said Kamien. “As we learn more about these systems, we’re going to be able to make these kinds of lenses to order and use them to direct light.”
This type of directed assembly could be useful in making optical switches and in other applications.
Their work was published in Physical Review X (open access) and was supported by the National Science Foundation, Penn’s Materials Science Research and Engineering Center and the Simons Foundation.

Abstract of Physical Review X paper
Focal conic domains (FCDs) in smectic-A liquid crystals have drawn much attention, both for their exquisitely structured internal form and for their ability to direct the assembly of micromaterials and nanomaterials in a variety of patterns. A key to directing FCD assembly is control over the eccentricity of the domain. Here, we demonstrate a new paradigm for creating spatially varying FCD eccentricity by confining a hybrid-aligned smectic with curved interfaces. In particular, we manipulate interface behavior with colloidal particles in order to experimentally produce two examples of what has recently been dubbed the flower texture [C. Meyer et al., Focal Conic Stacking in Smectic A Liquid Crystals: Smectic Flower and Apollonius Tiling, Materials 2, 499, 2009], where the focal hyperbolæ diverge radially outward from the center of the texture, rather than inward as in the canonical éventail or fan texture. We explain how this unconventional assembly can arise from appropriately curved interfaces. Finally, we present a model for this system that applies the law of corresponding cones, showing how FCDs may be embedded smoothly within a “background texture” of large FCDs and concentric spherical layers, in a manner consistent with the qualitative features of the smectic flower. Such understanding could potentially lead to disruptive liquid-crystal technologies beyond displays, including patterning, smart surfaces, microlens arrays, sensors, and nanomanufacturing.

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Graphene + magnetic field creates exotic new quantum electronic states

Could make graphene suitable for quantum computing for high-priority computational tasks
December 26, 2013
On a piece of graphene (the dark horizontal surface with a hexagonal pattern of carbon atoms), in a strong magnetic field, electrons can move only along the edges, and are blocked from moving in the interior. In addition, only electrons with one direction of spin can move in only one direction along the edges (indicated by the white-on-blue arrows), while electrons with the opposite spin are blocked (as shown by the white-on-red arrows). (Credit: A. F. Young et al.)
MIT research has found additional potential for graphene that could make it suitable for exotic uses such as quantum computing.
Under an extremely powerful magnetic field and at extremely low temperature, the researchers found, graphene can effectively filter electrons according to the direction of their spin, something that cannot be done by any conventional electronic system.
The trick:
  • Turn on a powerful magnetic field perpendicular to the graphene flake. That causes current to flows only along the edge, and flows only in one direction — clockwise or counterclockwise, depending on the orientation of the magnetic field — in a phenomenon known as the quantum Hall effect.
  • Turn on a second magnetic field — this time in the same plane as the graphene flake. Graphene’s behavior changes yet again: electrons can now move in either direction around the conducting edge; electrons that have one kind of spin move clockwise while those with the opposite spin move counterclockwise.
Making circuits and transistors
“We created an unusual kind of conductor along the edge, virtually a one-dimensional wire.” says Andrea Young, a Pappalardo Postdoctoral Fellow in MIT’s physics department and the paper’s lead author,  The segregation of electrons according to spin is “a normal feature of topological insulators,” he says, “but graphene is not normally a topological insulator. We’re getting the same effect in a very different material system.”
What’s more, by varying the magnetic field, “we can turn these edge states on and off,” Young says. That switching capability means that, in principle, “we can make circuits and transistors out of these,” he says, which has not been realized before in conventional topological insulators.
There is another benefit of this spin selectivity, Young says: It prevents a phenomenon called “backscattering,” which could disrupt the motion of the electrons. As a result, imperfections that would ordinarily ruin the electronic properties of the material have little effect. “Even if the edges are ‘dirty,’ electrons are transmitted along this edge nearly perfectly,” he says.
A graphene-based quantum computer
Professor Pablo Jarillo-Herrero , the Mitsui Career Development Associate Professor of Physics at MIT, says the behavior seen in these graphene flakes was predicted, but never seen before. This work, he says, is the first time such spin-selective behavior has been demonstrated in a single sheet of graphene, and also the first time anyone has demonstrated the ability “to transition between these two regimes.”
That could ultimately lead to a novel way of making a kind of quantum computer, Jarillo-Herrero says, something that researchers have tried to do, without success, for decades. But because of the extreme conditions required, Young says, “this would be a very specialized machine” used only for high-priority computational tasks, such as in national laboratories.
Ray Ashoori, a professor of physics, points out that the newly discovered edge states have a number of surprising properties. For example, although gold is an exceptionally good electrical conductor, when dabs of gold are added to the edge of the graphene flakes, they cause the electrical resistance to increase. The gold dabs allow the electrons to backscatter into the oppositely traveling state by mixing the electron spins; the more gold is added, the more the resistance goes up.
This research represents “a new direction” in topological insulators, Young says. “We don’t really know what it might lead to, but it opens our thinking about the kind of electrical devices we can make.”
The experiments required the use of a magnetic field with a strength of 35 tesla — “about 10 times more than in an MRI machine,” Jarillo-Herrero says — and a temperature of just 0.3 degrees Celsius above absolute zero. However, the team is already pursuing ways of observing a similar effect at magnetic fields of just one tesla and at higher temperatures.
Philip Kim, a professor of physics at Columbia University who was not involved in this work, says, “The authors here have beautifully demonstrated excellent quantization of the conductance,” as predicted by theory. He adds, “This is very nice work that may connect topological insulator physics to the physics of graphene with interactions. This work is a good example how the two most popular topics in condensed matter physics are connected each other.”
The research is published this week in the journal Nature.
The team also included researchers at the National Institute for Materials Science in Tsukuba, Japan. The work was supported by grants from the U.S. Department of Energy, the Gordon and Betty Moore Foundation, and the National Science Foundation, and used facilities at the National High Magnetic Field Laboratory in Florida.

Abstract of Nature paper
Low-dimensional electronic systems have traditionally been obtained by electrostatically confining electrons, either in heterostructures or in intrinsically nanoscale materials such as single molecules, nanowires and graphene. Recently, a new method has emerged with the recognition that symmetry-protected topological (SPT) phases, which occur in systems with an energy gap to quasiparticle excitations (such as insulators or superconductors), can host robust surface states that remain gapless as long as the relevant global symmetry remains unbroken. The nature of the charge carriers in SPT surface states is intimately tied to the symmetry of the bulk, resulting in one- and two-dimensional electronic systems with novel properties. For example, time reversal symmetry endows the massless charge carriers on the surface of a three-dimensional topological insulator with helicity, fixing the orientation of their spin relative to their momentum. Weakly breaking this symmetry generates a gap on the surface, resulting in charge carriers with finite effective mass and exotic spin textures. Analogous manipulations have yet to be demonstrated in two-dimensional topological insulators, where the primary example of a SPT phase is the quantum spin Hall state. Here we demonstrate experimentally that charge-neutral monolayer graphene has a quantum spin Hall state when it is subjected to a very large magnetic field angled with respect to the graphene plane. In contrast to time-reversal-symmetric systems, this state is protected by a symmetry of planar spin rotations that emerges as electron spins in a half-filled Landau level are polarized by the large magnetic field. The properties of the resulting helical edge states can be modulated by balancing the applied field against an intrinsic antiferromagnetic instability, which tends to spontaneously break the spin-rotation symmetry. In the resulting canted antiferromagnetic state, we observe transport signatures of gapped edge states, which constitute a new kind of one-dimensional electronic system with a tunable bandgap and an associated spin texture.

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New data-compression method reduces big-data bottleneck

Outperforms and enhances JPEG, handles both analog and digital signals
December 26, 2013
UCLA researchers compressed data using “warping,” resembling the graphic art technique of anamorphism (credit: UCLA)
A new “warping” data compression method that outperforms existing techniques has been developed byUCLA Henry Samueli School of Engineering and Applied Science researchers, based on the graphic art technique of anamorphism.
The JALALI-LAB group, led by Bahram Jalali, holder of the Northrop Grumman Opto-Electronic Chair in Electrical Engineering, discovered that it is possible to achieve data compression by stretching and warping the data using a new “anamorphic stretch transform” (AST) technique, which operates both in analog and digital domains.
In analog applications, AST makes it possible to not only capture and digitize signals that are faster than the speed of the sensor and the digitizer, but also to minimize the volume of data generated in the process.
AST can also compress digital records — for example, medical data, so it can be transmitted over the Internet for a tele-consultation. The transformation causes the signal to be reshaped is such a way that “sharp” features — its most defining characteristics — are stretched more than data’s “coarse” features.
The technique does not require prior knowledge of the data for the transformation to take place; it occurs naturally and in a streaming fashion.
“Our transformation causes feature-selective stretching of the data and allocation of more pixels to sharper features where they are needed the most,” Asghari said. “For example, if we used the technique to take a picture of a sailboat on the ocean, our anamorphic stretch transform would cause the sailboat’s features to be stretched much more than the ocean, to identify the boat while using a small file size.”
Outperforms JPEG
AST can also be used for image compression, as a standalone algorithm or combined with existing digital compression techniques to enhance speed or quality or to improve the amount images can be compressed. Results have shown that AST can outperform standard JPEG image compression format, with dramatic improvement in terms of image quality and compression factor.
The new technique has its origin in another technology pioneered by the Jalali group, time stretch dispersive Fourier transform, which is a method for slowing down and amplifying faint but very fast signals so they can be detected and digitized in real time.
High-speed instruments created with this technology enabled the discovery of optical rogue waves in 2007 and the detection of cancer cells in blood with one-in-a-million sensitivity in 2012. But these instruments produce a fire hose of data that overwhelms even the most advanced computers. The need to deal with such data loads motivated the UCLA team to search for a new data compression technology.
“Reshaping the data by stretching and wrapping it in the prescribed manner compresses it without losing pertinent information,” he said. “It emulates what happens to waves as they travel through physical media with specific properties. It also brings to mind aspects of surrealism and the optical effects of anamorphism.”
Asghari was supported by a grant from the Natural Sciences and Engineering Research Council of Canada. Jalali also has UCLA faculty appointments in bioengineering and in the David Geffen School of Medicine’s department of surgery, and he is a member of the California NanoSystems Institute.

Abstract of Applied Optics paper
A general method for compressing the modulation time–bandwidth product of analog signals is introduced. As one of its applications, this physics-based signal grooming, performed in the analog domain, allows a conventional digitizer to sample and digitize the analog signal with variable resolution. The net result is that frequency components that were beyond the digitizer bandwidth can now be captured and, at the same time, the total digital data size is reduced. This compression is lossless and is achieved through a feature selective reshaping of the signal’s complex field, performed in the analog domain prior to sampling. Our method is inspired by operation of Fovea centralis in the human eye and by anamorphic transformation in visual arts. The proposed transform can also be performed in the digital domain as a data compression algorithm to alleviate the storage and transmission bottlenecks associated with “big data.”

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The best neuroscience images of 2013

December 27, 2013
(Credit: Cai et al. Nature Methods)
The brain bank science blog (by a group of Manchester, UK-based scientists) has posted 12 images from 2013 that are as much fantastic works of art as neuroscience. Shown here: “Brainbow,” a transgenic system designed to label different types of brain cells in a festive panoply of colors.

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Reflected hidden faces in photographs revealed in pupil

What do your Instagram and Facebook photos reveal?
December 27, 2013
Zooming in on the pupil of a subject’s eye reveals hidden bystanders (credit: Rob Jenkins)
The pupil* of the eye in a photograph of a face can be mined for hidden information, such as reflected faces of the photographer and bystanders, according to research led by Dr. Rob Jenkins, of the Department of Psychology at the University of York and published in PLOS ONE (open access).
The researchers say that in crimes in which the victims are photographed, such as hostage taking or child sex abuse, reflections in the eyes of the photographic subject could help to identify perpetrators. Images of people retrieved from cameras seized as evidence during criminal investigations could be used to piece together networks of associates or to link individuals to particular locations.
By zooming in on high-resolution passport-style photographs, Jenkins and co-researcher Christie Kerr of the School of Psychology, University of Glasgow were able to recover bystander images that could be identified accurately by observers, despite their low resolution.
Lineup-style array of reflected images from photographs for spontaneous recognition task in experiment. All participants were familiar with the face of the psychologist and unfamiliar with the faces of the bystanders. Correct naming of the familiar face was frequent (hits 90%), and mistaken identification of the unfamiliar faces was infrequent (false positives 10%). (Credit: Rob Jenkins)
To establish whether these bystanders could be identified from the reflection images, the researchers presented them as stimuli in a face-matching task. Observers who were unfamiliar with the bystanders’ faces performed at 71 per cent accuracy, while participants who were familiar with the faces performed at 84 per cent accuracy. In a test of spontaneous recognition, observers could reliably name a familiar face from an eye reflection image.
“The pupil of the eye is like a black mirror,” said Jenkins. “To enhance the image, you have to zoom in and adjust the contrast. A face image that is recovered from a reflection in the subject’s eye is about 30,000 times smaller than the subject’s face.” In the research, the whole-face area for the reflected bystanders was 322 pixels on average.
Forensics implications
You probably recognize this well-known person, even though his face in this image measures only 16 pixels wide × 20 pixels high. (Photo credit: Steve Jurvetson)
High-resolution face photographs may also contain unexpected information about the environment of the photographic subject, including the appearance of the immediate surroundings, Jenkins explained to KurzweilAI.
“In the context of criminal investigations, this could be used to piece together networks of associates, or to link individuals to particular locations. This may be especially important when for categories of crime in which perpetrators photograph their victims. Reflections in the victims eyes could reveal the identity of the photographer.
“Also, around 40 million photographs per day are uploaded to Instagram alone, he pointed out. “Faces are among the most frequently photographed objects. Our study serves as a reminder to be careful what you upload. Eyes in the photographs could reveal where you were and who you were with.”
Although Jenkins did the study with a high-resolution (39 megapixels) Hasselblad camera, face images retrieved from eye reflections need not be of high quality in order to be identifiable, he said. “Obtaining optimal viewers — those who are familiar with the faces concerned — may be more important than obtaining optimal images.”
In addition, “in accordance with Hendy’s Law (a derivative of Moore’s Law), pixel count per dollar for digital cameras has been doubling approximately every twelve months. This trajectory implies that mobile phones could soon carry >39 megapixel cameras routinely.”
It would be interesting to see what hidden information is buried in law-enforcement (and other) photo archives — some of which could even help exculpate innocent persons.
*Technically, the image is reflected by the cornea.

Abstract of PLOS ONE paper
Criminal investigations often use photographic evidence to identify suspects. Here we combined robust face perception and high-resolution photography to mine face photographs for hidden information. By zooming in on high-resolution face photographs, we were able to recover images of unseen bystanders from reflections in the subjects’ eyes. To establish whether these bystanders could be identified from the reflection images, we presented them as stimuli in a face matching task (Experiment 1). Accuracy in the face matching task was well above chance (50%), despite the unpromising source of the stimuli. Participants who were unfamiliar with the bystanders’ faces (n = 16) performed at 71% accuracy [t(15) = 7.64, p<.0001, d = 1.91], and participants who were familiar with the faces (n = 16) performed at 84% accuracy [t(15) = 11.15, p<.0001, d = 2.79]. In a test of spontaneous recognition (Experiment 2), observers could reliably name a familiar face from an eye reflection image. For crimes in which the victims are photographed (e.g., hostage taking, child sex abuse), reflections in the eyes of the photographic subject could help to identify perpetrators.

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Friday, December 20, 2013

Converting algae to crude oil — a million-year natural process — in minutes

December 20, 2013
Algae slurry (credit: PNNL)
Engineers at the Department of Energy’s Pacific Northwest National Laboratory have created a continuous chemical process that produces useful crude oil from harvested algae in minutes, described in the journal Algae Research.
Utah-based Genifuel Corp. has licensed the technology and is working with an industrial partner to build a pilot plant using the technology.
How to create ‘instant oil’
(L-R): Algae slurry, biocrude oil, and (with further processing) refined biocrude, which contains mostly the makings of gasoline and diesel fuel (credit: PNNL)
A slurry of wet algae is pumped into the front end of a chemical reactor. Once the system is up and running, out comes crude oil in less than an hour. With additional conventional refining, the crude algae oil is converted into aviation fuel, gasoline, or diesel fuel.
The process also creates waste water — which is processed further, yielding burnable gas — and substances like potassium and nitrogen, which, along with the cleansed water, can also be recycled to grow more algae.
Process scheme utilizing algae growth and hydrothermal processing for fuel (credit: PNNL)
While algae has long been considered a potential source of biofuel, and several companies have produced algae-based fuels on a research scale, the fuel has been projected to be expensive. The PNNL technology harnesses algae’s energy potential efficiently and incorporates a number of methods to reduce the cost of producing algae fuel.
Eliminating slow, energy-inefficient drying and hexane steps
PNNL scientists and engineers simplified the production of crude oil from algae by combining several chemical steps into one continuous process. The most important cost-saving step is that the process works with wet algae. Most current processes require the algae to be dried — a process that takes a lot of energy and is expensive. The new process works with an algae slurry that contains as much as 80 to 90 percent water.
While a few other groups have tested similar processes to create biofuel from wet algae, most of that work is done one batch at a time. The PNNL system runs continuously, processing about 1.5 liters of algae slurry in the research reactor per hour. While that doesn’t seem like much, it’s much closer to the type of continuous system required for large-scale commercial production.
The PNNL system also eliminates another step required in today’s most common algae-processing method: the need for complex processing with solvents like hexane to extract the energy-rich oils from the rest of the algae. Instead, the PNNL team works with the whole algae, subjecting it to very hot water under high pressure to tear apart the substance, converting most of the biomass into liquid and gas fuels.
Pressure cooker
The system runs at around 350 degrees Celsius (662 degrees Fahrenheit) at a pressure of around 3,000 PSI, combining processes known as hydrothermal liquefaction and catalytic hydrothermal gasification. Elliott says such a high-pressure system is not easy or cheap to build, which is one drawback to the technology, though the cost savings on the back end more than makes up for the investment.
“It’s a bit like using a pressure cooker, only the pressures and temperatures we use are much higher,” said Douglas Elliott, the laboratory fellow who led the PNNL team’s research. “In a sense, we are duplicating the process in the Earth that converted algae into oil over the course of millions of years. We’re just doing it much, much faster.”
The recent work is part of DOE’s National Alliance for Advanced Biofuels & Bioproducts (NAABB), funded with American Recovery and Reinvestment Act funds by DOE’s Office of Energy Efficiency and Renewable Energy. Both PNNL and Genifuel have been partners in the NAABB program.

Abstract of Algal Research paper
Wet algae slurries can be converted into an upgradeable biocrude by hydrothermal liquefaction (HTL). High levels of carbon conversion to gravity separable biocrude product were accomplished at relatively low temperature (350 °C) in a continuous-flow, pressurized (sub-critical liquid water) environment (20 MPa). As opposed to earlier work in batch reactors reported by others, direct oil recovery was achieved without the use of a solvent and biomass trace components were removed by processing steps so that they did not cause process difficulties. High conversions were obtained even with high slurry concentrations of up to 35 wt.% of dry solids. Catalytic hydrotreating was effectively applied for hydrodeoxygenation, hydrodenitrogenation, and hydrodesulfurization of the biocrude to form liquid hydrocarbon fuel. Catalytic hydrothermal gasification was effectively applied for HTL byproduct water cleanup and fuel gas production from water soluble organics, allowing the water to be considered for recycle of nutrients to the algae growth ponds. As a result, high conversion of algae to liquid hydrocarbon and gas products was found with low levels of organic contamination in the byproduct water. All three process steps were accomplished in bench-scale, continuous-flow reactor systems such that design data for process scale-up was generated.

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World’s first text message via molecular communication sent

May be useful for communication underground, underwater, or inside the body
December 20, 2013
Molecular transmitter: letters are entered in the  LCD Shield Kit and encoded in the Arduino Uno board as a binary sequence of five bits (e.g., E = 10000, using the least number of 1′s) and each bit is sent to the spray device to spray (1) or not spray (0) isopropyl alcohol, propagated by a fan (credit: N. Farsad et al./PLOS ONE)
Scientists have created a molecular communications system for the transmission of messages and data in challenging environments where electromagnetic waves cannot be used — such as tunnels, pipelines, underwater, within the body, and in biomedical nanorobots.
Molecular signaling is a common feature of the plant and animal kingdom — insects for example use pheromones for long-range signalling — but to date, continuous data have not been transmitted using this method.
Researchers at the University of Warwick in the UK and the York University in Canada have developed the capability to transform any generic message into binary signals. These are in turn “programmed” into evaporated alcohol molecules to demonstrate the potential of molecular communications.
Their results are published in the open-access journal PLOS ONE.
World’s first text message via molecular communication
Molecular receiver: one of three sensors (for various types of tests) demodulates the incoming signal by assigning the bit 1 to increasing concentration and 0 to decreasing. The binary data is converted back to letters in the Arduino board and sent via serial port to a computer for display. (Credit: N. Farsad et al./PLOS ONE)
The first demonstration signal, performed in Canada, was “O Canada,” from the Canadian national anthem. It was sent several meters across open space before it was decoded by a receiver. The hardware is made from off-the-shelf electronics and costs around $100.
“We believe we have sent the world’s first text message to be transmitted entirely with molecular communication, controlling concentration levels of the alcohol molecules, to encode the alphabets with single spray representing bit 1 and no spray representing the bit 0,” said York doctoral candidate Nariman Farsad, who led the experiment.
“Imagine sending a detailed message using perfume — it sounds like something from a spy thriller novel, but in reality it is an incredibly simple way to communicate,” said Dr. Weisi Guo from the School of Engineering at the University of Warwick.
Molecular receiver flowchart (credit: N. Farsad et al./PLOS ONE)
“Of course, signaling or cues are something we see all the time in the natural world — bees for example use chemicals in pheromones to signal to others when there is a threat to the hive, and people have achieved short-range signaling using chemicals.
“But we have gone to the next level and successfully communicated continuous and generic messages over several meters.
“Potential targeted applications include wireless monitoring of sewage works and oil rigs. This could prevent future disasters such as the bus-sized fatberg found blocking the London sewage networks in 2013, and the Deepwater Horizon oil spill in 2010.
“They can also be used to communicate on the nanoscale, for example, in medicine, where recent advances mean it’s possible to embed sensors into the organs of the body or create miniature robots to carry out a specific task, such as targeting drugs to cancer cells.
“On these tiny scales and in special structural environments, there are constraints with electromagnetic signals such as the ratio of antenna size to the wavelength of the signal, which chemical communication does not have. Molecular communication signals are also biocompatible and require very little energy to generate and propagate.”
The team will now set up a company that aims to bring a range of academic and industrial products to the market within 6 months to 1 year, Guo told KurzweilAI.

Abstract of PLOS ONE paper
In this work, we describe the first modular, and programmable platform capable of transmitting a text message using chemical signalling – a method also known as molecular communication. This form of communication is attractive for applications where conventional wireless systems perform poorly, from nanotechnology to urban health monitoring. Using examples, we demonstrate the use of our platform as a testbed for molecular communication, and illustrate the features of these communication systems using experiments. By providing a simple and inexpensive means of performing experiments, our system fills an important gap in the molecular communication literature, where much current work is done in simulation with simplified system models. A key finding in this paper is that these systems are often nonlinear in practice, whereas current simulations and analysis often assume that the system is linear. However, as we show in this work, despite the nonlinearity, reliable communication is still possible. Furthermore, this work motivates future studies on more realistic modelling, analysis, and design of theoretical models and algorithms for these systems.

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Method for mass production of graphene-based field-effect transistors (FETs) developed

December 20, 2013
Schematic representation of the formation of BCN-graphene via solvothermal reaction between carbon tetrachloride (CCl4), boron tribromide (BBr3), and nitrogen (N2) in the presence of potassium (K). Photograph is of the autoclave after the reaction, showing the formation of BCN-graphene (black) and potassium halide (KCl and KBr, white). (Credit: UNIST)
Ulsan National Institute of Science and Technology (UNIST) researchers in Korea have announced a method for mass production of graphene-based field-effect transistors (FETs).
The design creates boron/nitrogen co-doped graphene nanoplatelets (BCN-graphene) via a simple solvothermal reaction of BBr3/CCl4/N2 in the presence of potassium.
Various methods of making graphene-based FETs have been exploited, including doping graphene, tailoring graphene like a nanoribbon, and using boron nitride as a support, the researchers said.
Among the methods of controlling the bandgap* of graphene, doping methods show the most promise in terms of industrial-scale feasibility, they suggest.
Researchers have previously tried to add boron to graphene to open its bandgap to achieve semiconductor performance, without success, because the atomic size of boron, 85 pm (atomic radius) is larger than that of carbon (77 pm).
Now, the UNIST researcher team, led by Prof. Jong-Beom Baek, has found that boron/nitrogen co-doping is only feasible when carbon tetrachloride (CCl4 ) is treated with boron tribromide (BBr3 ) and nitrogen (N2) gas, which at 70 pm is a bit smaller than carbon and boron.
Pairing two nitrogen atoms and two boron atoms can compensate for the atomic size mismatch, so boron and nitrogen pairs can be easily introduced into the graphitic network, the researchers say. The resultant BCN-graphene generates a bandgap appropriate for FETs.
“Although the performance of the FET is not in the range of commercial silicon-based semiconductors, this initiative work should be the proof of a new concept and a great leap forward for studying graphene with bandgap opening,” said Baek. “Now, the remaining challenge is fine-tuning a bandgap to improve the on/off current ratio for real device applications.”
This work will be published in Angewandte Chemie International Edition as a VIP (“very important paper”).
The research work was funded by the National Research Foundation (NRF) of Korea and the U.S. Air Force Office of Scientific Research through the Asian Office of Aerospace R&D (AFOSR-AOARD).
* A bandgap is the energy required to allow an electron to move freely within a solid material — a major factor determining the electrical conductivity of a solid. Substances with large band gaps are generally insulators; conductors (such as native graphene) either have very small band gaps or none. Those with intermediate bandgaps are semiconductors.

Abstract of Angewandte Chemie International Edition paper
Boron/nitrogen co-doped graphene (BCN graphene) is directly synthesized from a reaction between CCl4/BBr3/N2 in the presence of potassium. The reaction of CCl4 with either BBr3 or N2 alone leads to a marginally doped graphene. On the other hand, there is a synergistic effect when CCl4 is reacted with BBr3 and N2 together to yield BCN graphene. The resultant BCN graphene displays good dispersion stability in N-methyl-2-pyrrolidone, allowing for the fabrication of a field-effect transistor by solution casting, which displays an on/off ratio of 10.7 with an optical band gap of 3.3 eV. Considering the scalability and solution processability, BCN graphene has a high potential for many practical applications.

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A new — and reversible — cause of aging

NAD, a naturally produced compound in cells, rewinds aspects of age-related demise in mice
December 20, 2013
Sirt1 protein, red, circles the cell’s chromosomes, blue (credit: Ana Gomes)
Researchers have discovered a cause of aging in mammals that may be reversible: a series of molecular events that enable communication inside cells between the nucleus and mitochondria.
As communication breaks down, aging accelerates. By administering a molecule naturally produced by the human body, scientists restored the communication network in older mice. Subsequent tissue samples showed key biological hallmarks that were comparable to those of much younger animals.
“The aging process we discovered is like a married couple — when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down,” said Harvard Medical School Professor of Genetics David Sinclair, senior author on the study. “And just like with a couple, restoring communication solved the problem.”
This study was a joint project between Harvard Medical School, the National Institute on Aging, and the University of New South Wales, Sydney, Australia, where Sinclair also holds a position.
The findings were published Dec. 19 in Cell.
When Sirt1 loses its ability to monitor HIF-1, communication between mitochondria and the nucleus breaks down, and aging accelerates (credit: Ana Gomes)
Communication breakdown
Mitochondria are often referred to as the cell’s “powerhouse,” generating chemical energy to carry out essential biological functions. These self-contained organelles, which live inside our cells and house their own small genomes, have long been identified as key biological players in aging.
But as they become increasingly dysfunctional over time, many age-related conditions such as Alzheimer’s disease and diabetes gradually set in.
Researchers have generally been skeptical of the idea that aging can be reversed, due mainly to the prevailing theory that age-related ills are the result of mutations in mitochondrial DNA — and mutations cannot be reversed.
Sinclair and his group have been studying the fundamental science of aging — which is broadly defined as the gradual decline in function with time — for many years, primarily focusing on a group of genes called sirtuins. Previous studies from his lab showed that one of these genes, SIRT1, was activated by the compound resveratrol, which is found in grapes, red wine and certain nuts.
Ana Gomes, a postdoctoral scientist in the Sinclair lab, had been studying mice in which this SIRT1 gene had been removed. While they accurately predicted that these mice would show signs of aging, including mitochondrial dysfunction, the researchers were surprised to find that most mitochondrial proteins coming from the cell’s nucleus were at normal levels; only those encoded by the mitochondrial genome were reduced.
“This was at odds with what the literature suggested,” said Gomes.
Reversing aging by restoring NAD
As Gomes and her colleagues investigated potential causes for this, they discovered an intricate cascade of events that begins with a chemical called NAD and concludes with a key molecule that shuttles information and coordinates activities between the cell’s nuclear genome and the mitochondrial genome. Cells stay healthy as long as coordination between the genomes remains fluid. SIRT1’s role is intermediary, akin to a security guard; it assures that a meddlesome molecule called HIF-1 does not interfere with communication.
For reasons still unclear, as we age, levels of the initial chemical NAD decline. Without sufficient NAD, SIRT1 loses its ability to keep tabs on HIF-1. Levels of HIF-1 escalate and begin wreaking havoc on the otherwise smooth cross-genome communication. Over time, the research team found, this loss of communication reduces the cell’s ability to make energy, and signs of aging and disease become apparent.
“This particular component of the aging process had never before been described,” said Gomes.
While the breakdown of this process causes a rapid decline in mitochondrial function, other signs of aging take longer to occur. Gomes found that by administering an endogenous compound that cells transform into NAD, she could repair the broken network and rapidly restore communication and mitochondrial function. If the compound was given early enough — prior to excessive mutation accumulation — within days, some aspects of the aging process could be reversed.
HIF-1: a cancer-aging connection
Examining muscle from two-year-old mice that had been given the NAD-producing compound for just one week, the researchers looked for indicators of insulin resistance, inflammation, and muscle wasting. In all three instances, tissue from the mice resembled that of six-month-old mice. In human years, this would be like a 60-year-old converting to a 20-year-old in these specific areas.
One particularly important aspect of this finding involves HIF-1. More than just an intrusive molecule that foils communication, HIF-1 normally switches on when the body is deprived of oxygen. Otherwise, it remains silent. Cancer, however, is known to activate and hijack HIF-1. Researchers have been investigating the precise role HIF-1 plays in cancer growth.
“It’s certainly significant to find that a molecule that switches on in many cancers also switches on during aging,” said Gomes. “We’re starting to see now that the physiology of cancer is in certain ways similar to the physiology of aging. Perhaps this can explain why the greatest risk of cancer is age.”
“There’s clearly much more work to be done here, but if these results stand, then certain aspects of aging may be reversible if caught early,” said Sinclair.
The researchers are now looking at the longer-term outcomes of the NAD-producing compound in mice and how it affects the mouse as a whole. They are also exploring whether the compound can be used to safely treat rare mitochondrial diseases or more common diseases such as Type 1 and Type 2 diabetes. Longer term, Sinclair plans to test if the compound will give mice a healthier, longer life.
The Sinclair lab is funded by the National Institute on Aging (NIA/NIH), the Glenn Foundation for Medical Research, the Juvenile Diabetes Research Foundation, the United Mitochondrial Disease Foundation and a gift from the Schulak family.

Abstract of Cell paper
  • A specific decline in mitochondrially encoded genes occurs during aging in muscle
  • Nuclear NAD+ levels regulate mitochondrial homeostasis independently of PGC-1α/β
  • Declining NAD+ during aging causes pseudohypoxia, which disrupts OXPHOS function
  • Raising nuclear NAD+ in old mice reverses pseudohypoxia and metabolic dysfunction
Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD+ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible.

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Thursday, December 19, 2013

Music brings memories back to the injured brain

December 19, 2013
(Credit: iStockphoto)
New hope for severely brain-injured patients: researchers have found that playing popular music can help them recall personal memories.
The study by Amee Baird and Séverine Samson, published in Neuropsychological Rehabilitation (open access), is the first to examine what they call “music-evoked autobiographical memories” (MEAMs) in patients with acquired brain injuries.
The researchers played excerpts from 50 “Number 1 Songs of the Year” (from 1960 to 2010) and found that the frequency of recorded MEAMs was similar for patients and controls.
They found that approximately 30% of the songs elicited autobiographical memories that were typically of a person or people, or a period of life. Analysis of written memory reports found that the most common situations associated with MEAMs was “dancing” or “driving a car,” and the most common social reference was “friends,” followed by “girl/boyfriends.”
The study covered only five patients without a fundamental deficit in autobiographical recall memory (such as Alzheimer’s) and with intact pitch perception.

Abstract of Neuropsychological Rehabilitation paper
Music evoked autobiographical memories (MEAMs) have been characterised in the healthy population, but not, to date, in patients with acquired brain injury (ABI). Our aim was to investigate music compared with verbal evoked autobiographical memories. Five patients with severe ABI and matched controls completed the experimental music (MEAM) task (a written questionnaire) while listening to 50 “Number 1 Songs of the Year” (from 1960 to 2010). Patients also completed the Autobiographical Memory Interview (AMI) and a standard neuropsychological assessment. With the exception of Case 5, who reported no MEAMs and no autobiographical incidents on the AMI and who also had impaired pitch perception, the range of frequency and type of MEAMs in patients was broadly in keeping with their matched controls. The relative preservation of MEAMs in four cases was particularly noteworthy given their impaired verbal and/or visual anterograde memory, and in three cases, autobiographical memory impairment. The majority of MEAMs in both cases and matched controls were of a person/people or a period of life. In three patients music was more efficient at evoking autobiographical memories than the AMI verbal prompts. This is the first study of MEAMs after ABI. The findings suggest that music is an effective stimulus for eliciting autobiographical memories, and may be beneficial in the rehabilitation of autobiographical amnesia, but only in patients without a fundamental deficit in autobiographical recall memory and intact pitch perception.

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Programming smart molecules for chemical-based AI

Machine-learning algorithms could make chemical reactions intelligent, tuned to your personal chemistry to diagnose or treat a range of pathologies using "smart drugs"
December 19, 2013
Inference at different levels of abstraction. (a) Factor graph over two random variables. Inference can be performed efficiently by passing messages (shown as gray arrows) between vertices. (b) Message passing implemented at a lower level of abstraction. (c) Schematic representation of DNA strand displacement. (Credit: Nils E. Napp and Ryan Prescott Adams)
Computer scientists at the Harvard School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University have joined forces to put powerful probabilistic reasoning algorithms in the hands of bioengineers.
In a new paper (open access) presented at the recent Neural Information Processing Systems conference, Ryan P. Adams and Nils Napp showed that an important class of artificial intelligence algorithms could be implemented using chemical reactions.
These algorithms, which use a technique called “message passing inference on factor graphs,” are a mathematical coupling of ideas from graph theory and probability. They represent the state of the art in machine learning and are already critical components of everyday tools ranging from search engines and fraud detection to error correction in mobile phones.
‘Smart drugs’
Adams’ and Napp’s work demonstrates that some aspects of artificial intelligence (AI) could be implemented at microscopic scales using molecules. In the long term, the researchers say, such theoretical developments could open the door for “smart drugs” that can automatically detect, diagnose, and treat a variety of diseases using a cocktail of chemicals that can perform AI-type reasoning.
“We understand a lot about building AI systems that can learn and adapt at macroscopic scales; these algorithms live behind the scenes in many of the devices we interact with every day,” says Adams, an assistant professor of computer science at SEAS, whose Intelligent Probabilistic Systems group focuses on machine learning and computational statistics.
“This work shows that it is possible to also build intelligent machines at tiny scales, without needing anything that looks like a regular computer. This kind of chemical-based AI will be necessary for constructing therapies that sense and adapt to their environment. The hope is to eventually have drugs that can specialize themselves to your personal chemistry and can diagnose or treat a range of pathologies.”
Adams and Napp designed a tool that can take probabilistic representations of unknowns in the world (probabilistic graphical models, in the language of machine learning) and compile them into a set of chemical reactions that estimate quantities that cannot be observed directly. The key insight is that the dynamics of chemical reactions map directly onto the two types of computational steps that computer scientists would normally perform in silico to achieve the same end.
Statistical inference by biological reaction pathways and regulatory networks
This insight opens up interesting new questions for computer scientists working on statistical machine learning, such as how to develop novel algorithms and models that are specifically tailored to tackling the uncertainty molecular engineers typically face. In addition to the long-term possibilities for smart therapeutics, it could also open the door for analyzing natural biological reaction pathways and regulatory networks as mechanisms that are performing statistical inference.
Just like robots, biological cells must estimate external environmental states and act on them; designing artificial systems that perform these tasks could give scientists a better understanding of how such problems might be solved on a molecular level inside living systems.
“There is much ongoing research to develop chemical computational devices,” says Napp, a postdoctoral fellow at the Wyss Institute, working on the Bioinspired Robotics platform, and a member of the Self-organizing Systems Research group at SEAS. Both groups are led by Radhika Nagpal, the Fred Kavli Professor of Computer Science at SEAS and a Wyss core faculty member. At the Wyss Institute, a portion of Napp’s research involves developing new types of robotic devices that move and adapt like living creatures.
“What makes this project different is that, instead of aiming for general computation, we focused on efficiently translating particular algorithms that have been successful at solving difficult problems in areas like robotics into molecular descriptions,” Napp explains. “For example, these algorithms allow today’s robots to make complex decisions and reliably use noisy sensors. It is really exciting to think about what these tools might be able to do for building better molecular machines.”
Indeed, the field of machine learning is revolutionizing many areas of science and engineering. The ability to extract useful insights from vast amounts of weak and incomplete information is not only fueling the current interest in “big data,” but has also enabled rapid progress in more traditional disciplines such as computer vision, estimation, and robotics, where data are available but difficult to interpret. Bioengineers often face similar challenges, as many molecular pathways are still poorly characterized and available data are corrupted by random noise.
Using machine learning, these challenges can now be overcome by modeling the dependencies between random variables and using them to extract and accumulate the small amounts of information each random event provides.
“Probabilistic graphical models are particularly efficient tools for computing estimates of unobserved phenomena,” says Adams. “It’s very exciting to find that these tools map so well to the world of cell biology.”

Abstract of Neural Information Processing Systems paper
Recent work on molecular programming has explored new possibilities for computational abstractions with biomolecules, including logic gates, neural networks, and linear systems. In the future such abstractions might enable nanoscale devices that can sense and control the world at a molecular scale. Just as in macroscale robotics, it is critical that such devices can learn about their environment and reason under uncertainty. At this small scale, systems are typically modeled as chemical reaction networks. In this work, we develop a procedure that can take arbitrary probabilistic graphical models, represented as factor graphs over discrete random variables, and compile them into chemical reaction networks that implement inference. In particular, we show that marginalization based on sum-product message passing can be implemented in terms of reactions between chemical species whose concentrations represent probabilities. We show algebraically that the steady state concentration of these species correspond to the marginal distributions of the random variables in the graph and validate the results in simulations. As with standard sum-product inference, this procedure yields exact results for tree-structured graphs, and approximate solutions for loopy graphs.

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Microprinting low-cost artificial cells

Could serve as drug and gene delivery devices
December 19, 2013
Schematic representation of production of arrays of controlled-size artificial cells by combining hydrogel stamping and electroformation techniques
Easily manufactured, low-cost artificial cells manufactured using microprinting may one day serve as drug and gene delivery devices and in biomaterials, biotechnology and biosensing applications, according to a team of Penn State biomedical engineers.
These artificial cells will also allow researchers to explore actions that take place at the cell membrane.
“In a natural cell, so much is going on inside that it is extremely complex,” said Sheereen Majd, assistant professor of biomedical engineering. Understanding how drugs and pathogens cross the cell membrane barrier is essential in preventing disease and delivering drugs.
“With these artificial cells — liposomes — we have just the shell, which gives us the ability to dissect the events that happen at the membrane.”
Artificial cell arrays
Researchers have created artificial cells for quite some time, but Majd’s team is creating large arrays of artificial cells, made of lipids and proteins, of uniform size that can either remain attached to the substrate on which they grow, or become separated and used as freely moving vessels.
“The trend in the pharmaceutical industry today is that they like to do high-throughput screenings,” said Majd. “They could use a large number of these artificial cells all of the same size with the same conditions in an array and monitor many cells at once.”
The researchers’ cells are also different because they contain lipids with protein components, the way cell membranes exist in nature. The various proteins serve to allow certain materials to enter and leave the cell, acting as regulators.
“These giant proteoliposomes closely mimic cellular membranes,” said Majd. “So they are excellent model systems for studying processes that happen at the surface of cells such as the molecular events that occur when pathogens and drugs enter cells.”
Older methods of artificial cell creation used dried lipids, but to create cells with proteins, the system must remain moist because when proteins dry out, they become useless.
How to create an artificial cell
Using hydrogel stamping, a process that creates a stamp out of wet hydrogel that deposits dots of the lipid and protein mixture on the surface of the substrate, the researchers can lay out an array of potential artificial cell locations. They then apply an AC electric field to the substrate. Where the lipid and protein mixture exists, tiny bubbles form that eventually combine into one artificial cell. The result is an array of artificial cells neatly placed and spaced on the substrate.
“The AC electric field produces agitation that creates the tiny bubbles that merge to form the cells. This process is called electroformation,” said Majd.
The variety of lipids and proteins used can vary depending on the ultimate purpose of the artificial cells. The cells that form are between 20 and 50 microns, within the range of natural cells.
“The beauty of this method is that a lot of labs already use liposomes and electroformation,” said Majd. “However, traditionally, they do not have proteins attached.”
Another problem is the traditional method creates artificial cells in tens of sizes situated all over the place, she added. Other methods require complex devices such as microfluidics to create uniformly sized artificial cells. With the hydrogel stamping method, it is easy to control the size of artificial cells and to generate a large number of these cells efficiently.
The researchers would next like to incorporate more than just lipids and proteins into the artificial cells. One possibility is to bind potential drugs to the proteins and lipids.
The Charles E. Kaufman Foundation at the Pittsburgh Foundation helped support this work.

Abstract of Advanced Materials paper
S. Majd and co-workers report a simple approach for the preparation of cell-sized liposomes with integral membrane proteins on page 6834. In this approach, hydrogel-stamped lipid/protein deposits grow, upon application of an AC electric field, into giant liposomes of controlled size and composition. The resulting vesicles can be applied in membrane and protein studies as well as in biotechnology.

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