Quantum Mechanics  

Light behaves both as a particle and as a wave. Since the days of Einstein, scientists have been trying to directly observe both of these aspects of light at the same time. Now, scientists have succeeded in capturing the first-ever snapshot of this dual behavior.

Quantum mechanics tells us that light can behave simultaneously as a particle or a wave. However, there has never been an experiment able to capture both natures of light at the same time; the closest we have come is seeing either wave or particle, but always at different times. Taking a radically different experimental approach, Ecole polytechnique fédérale de Lausanne (EPFL) scientists have now been able to take the first ever snapshot of light behaving both as a wave and as a particle.

The breakthrough work is published in Nature Communications.

When UV light hits a metal surface, it causes an emission of electrons. Albert Einstein explained this “photoelectric” effect by proposing that light – thought to only be a wave – is also a stream of particles. Even though a variety of experiments have successfully observed both the particle- and wave-like behaviors of light, they have never been able to observe both at the same time.

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A research team led by Fabrizio Carbone at EPFL has now carried out an experiment with a clever twist: using electrons to image light. The researchers have captured, for the first time ever, a single snapshot of light behaving simultaneously as both a wave and a stream of particles particle.

"This experiment demonstrates that, for the first time ever, we can film quantum mechanics – and its paradoxical nature – directly. Being able to image and control quantum phenomena at the nanometer scale like this opens up a new route towards quantum computing."

The experiment is set up like this: A pulse of laser light is fired at a tiny metallic nanowire. The laser adds energy to the charged particles in the nanowire, causing them to vibrate. Light travels along this tiny wire in two possible directions, like cars on a highway. When waves traveling in opposite directions meet each other they form a new wave that looks like it is standing in place. Here, this standing wave becomes the source of light for the experiment, radiating around the nanowire.

This is where the experiment’s trick comes in: The scientists shot a stream of electrons close to the nanowire, using them to image the standing wave of light. As the electrons interacted with the confined light on the nanowire, they either sped up or slowed down. Using the ultrafast microscope to image the position where this change in speed occurred, Carbone’s team could now visualize the standing wave, which acts as a fingerprint of the wave-nature of light.

While this phenomenon shows the wave-like nature of light, it simultaneously demonstrated its particle aspect as well. As the electrons pass close to the standing wave of light, they “hit” the light’s particles, the photons. As mentioned above, this affects their speed, making them move faster or slower. This change in speed appears as an exchange of energy “packets” (quanta) between electrons and photons. The very occurrence of these energy packets shows that the light on the nanowire behaves as a particle.

“This experiment demonstrates that, for the first time ever, we can film quantum mechanics – and its paradoxical nature – directly,” says Fabrizio Carbone. In addition, the importance of this pioneering work can extend beyond fundamental science and to future technologies. As Carbone explains: “Being able to image and control quantum phenomena at the nanometer scale like this opens up a new route towards quantum computing.”




SOURCE  EPFL

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 Microscopy  

By combining STM with the spectroscopic versatility of synchrotron x-rays, researchers have achieved chemical fingerprinting of individual nickel clusters on a copper surface at a resolution of 2 nm, creating a powerful and versatile nanoscale imaging tool with exciting promise and potential for the materials and biological sciences.

Researchers from the U.S. Department of Energy's Argonne National Laboratory and Ohio University have devised a powerful technique that simultaneously resolves the chemical characterization and topography of nanoscale materials down to the height of a single atom.

"We have demonstrated a world record in the spatial resolution of chemical imaging using synchrotron x-ray scanning tunneling microscopy."

Working at the Center for Nanoscale Materials (CNM)/X-ray Science Division 26-ID beamline of the U.S. Department of Energy’s Advanced Photon Source, the researchers took advantage of some new technological innovations in the work.

The technique combines synchrotron X-rays (SX) and scanning tunneling microscopy (STM). In experiments, the researchers used SX as a probe and a nanofabricated smart tip of a STM as a detector.

Using this technique, researchers detected the chemical fingerprint of individual nickel clusters on a copper surface at a two-nanometer (nm) lateral resolution, and at the ultimate single atom height sensitivity. By varying the photon energy, the researchers used the difference in photoabsorption cross sections for nickel and the copper substrate to chemically image a single-nickel nanocluster - thus opening the door to new opportunities for chemical imaging of nanoscale materials. Until now, a spatial limit of about only 10-nm was attainable, and the researchers would simultaneously sample a large sample area.  The researchers have improved the spatial resolution to 2 nm.

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The work is published in the journal Nanoletters. “We have demonstrated a world record in the spatial resolution of chemical imaging using synchrotron x-ray scanning tunneling microscopy,” said Saw-Wai Hla, a co-author of the study.

“Imaging with direct chemical sensitivity has been a long-standing goal since scanning tunneling microscopes were developed during the 1980s,” said Volker Rose, a physicist in the X-ray Science Division. “It was very exciting when we obtained elemental contrast of a material at just one atomic layer height”.

"This is a marriage between two of the most powerful instruments of materials science," said Saw-Wai Hla, electronic and magnetic materials and devices group leader in Argonne's Nanoscience & Technology Division. "We now have an instrument that can perform the functions of STM and X-rays in a single setting, and therefore it has a great potential to revolutionize the materials characterization."

To conduct the experiment, researchers used the Center for Nanoscale Materials’ (CNM) beamline 26-ID at the Advanced Photon Source (APS), which is equipped with two collinear undulator devices that serve as the X-ray source and a double-crystal monochromater that selects the photon energy. The X-rays were passed through a beam chopper to quickly turn the beam on and off and then illuminate the tip/sample junction in the SX-STM. This enabled the very sensitive lock-in detection of the X-ray induced currents.

The experiment was conducted at room temperature, which is well suited for the needs of most physical, chemical, biological and nanomaterial applications. The team anticipates that even higher spatial resolution may become possible with a new instrument currently under development.

“The next step will be to extend the new technique to low temperatures,” notes Rose. “Our measurements indicate that atomic resolution may be achievable at 5 K (about negative 450 F).”


SOURCE  Argonne National Laboratory

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 Microscopy  

Nanolive’s new microscope technology offers unperturbed and hitherto unperceived insights into living cells.  Observations are completely non-invasive to the cell and allow resolving the cell’s parts down to sizes of 70nm.

N

anolive SA, a start-up company founded last year at the EPFL Innovation Park in Lausanne, Switzerland, has developed a revolutionary microscope which, for the very first time, allows the exploration of a living cell in 3D without damaging it.

"You really need to be able to look at living cells because life is animate — it’s what defines life."

While scientists may still obtain a finer resolution using an electron microscope, this approach cannot be used to examine cells which are alive. For a long time, it was believed to be impossible to look inside a living cell using light microscopes due to their physical limitations. This year’s Nobel Prize for chemistry was awarded to S. Hell, E. Betzing and W. Moerner, who did not believe these presumed limitations and made revolutionary discoveries in the field of fluorescent microscopy.

While their research was focused on the chemistry of single molecules and their pathways inside living cells, Nanolive focuses on the physical structure of the living cell itself.

Fig. Mouse reticular fibroblast imaged with the 3D Cell Explorer. 

As a result, Nanolive’s technology can offer unperturbed and hitherto unperceived insights into the living cell: no longer a need for any special procedures or intensive and time-consuming preparation. As no chemistry or marker is used at all, observations are completely non-invasive to the cell and allow resolving the cell’s parts down to sizes of 70nm. This discovery has been published in Nature Photonics in January 2013.

Below, left, is shown the example of a fixed fibroblast chemically stained to identify membrane (green) and nucleus (blue). To the right is the same cell imaged with Nanolive’s 3D Cell Explorer, stained only digitally. In the first case, the preparation procedure killed the cell and took more than four hours. Using Nanolive’s technology, the same result took just five minutes and would have been possible on unstained, living cells.

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“You really need to be able to look at living cells because life is animate — it’s what defines life,” Eric Betzig stated in a recent interview.

The 3D Cell Explorer caters to this desire by displaying the cell in a completely new way with a comprehensive representation of its morphology. Since the cell is the basis of all life on earth, this is a major milestone in the history of microscopy, which may change all the rules in the fields of education, biology, pharmaceutics and cosmetics in labs and industry.

Hell said that a close look can shed light on disease: “Any disease, in the end, can be boiled down to a malfunctioning of the cell,” he said. “And in order to understand what a disease actually means, you have to understand the cell and you have to understand the malfunction.”

The 3D Cell Explorer is based on an enabling technology that overcomes the limitations of light. Similar to a MRI/CT scan in hospitals for the human body, our product takes a complete tomographic image of the refractive index within the living cell. For the first time ever you can actually look inside the cell and discover its interior such as its nucleus and its organelles. Thanks to the 3D Cell Explorer, never again researchers will have to guess what happens inside a living cell. They will actually see and precisely measure the impact of stimuli and drugs on cells, thus enabling completely new fields of research and smarter products.

Nanolive just launched its brand new website: www.nanolive.ch including a direct web store and a cell gallery where to find more astonishing cell images and timelapse movies http://nanolive.ch/cell-gallery/.




SOURCE  Nanolive

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 Microscopy  

A new imaging platform called a “lattice light sheet”  is a significant leap forward for light microscopy. It captures high-resolution images rapidly and minimizes damage to cells, so it can image the three-dimensional activity of molecules, cells, and embryos in fine detail over longer periods than was previously possible.

Powerful new microscopes have dramatically sharpened biologists' focus on the molecules that animate and propel life. Now, a new imaging platform developed by Eric Betzig and colleagues at the Howard Hughes Medical Institute's Janelia Research Campus offers another leap forward for light microscopy. The new technology collects high-resolution images rapidly and minimizes damage to cells, meaning it can image the three-dimensional activity of molecules, cells, and embryos in fine detail over longer periods than was previously possible.

The developers of the new lattice light sheet microscope have teamed with cell and molecular biologists to produce stunning videos of biological processes across a range of sizes and time scales, from the movements of individual proteins to the development of entire animal embryos. The scientists, including postdoctoral researchers Bi-Chang Chen (now at the Research Center for Applied Sciences in Taiwan), Wesley Legant, and Kai Wang, described their new technology and its applications in the journal Science.

Betzig, one of three scientists sharing the 2014 Nobel Prize in Chemistry, has developed a suite of new imaging technologies over the last decade. The techniques have improved biologists' ability to visually track the movements of cells' tiniest structures – but there were always trade-offs. Imaging cells at high resolution in three dimensions usually meant sacrificing imaging speed, as well as subjecting cells to significant light-induced toxicity.

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The video above shows five different stages during the division of a HeLa cell as visualized by the lattice light sheet microscope. Credit: Betzig Lab, HHMI/Janelia Research Campus; Mimori-Kiyosue Lab, RIKEN Center for Developmental Biology; published in Science

“What happens is you end up designing the questions you ask around the tools that are available,” Legant says. With the lattice light sheet, the Betzig team can now optimize their imaging technology for the questions that biologists want to answer.

The new microscope evolved from one Betzig unveiled in 2011. The Bessel beam plane illumination microscope illuminates samples with a virtual sheet of light, created when a beam of non-diffracting light called a Bessel beam sweeps across the imaging field. It produces high-resolution images with less light damage than a traditional microscope, and is fast enough to record dynamic processes in living cells.

Betzig's team had to incorporate a few tricks into that microscope to address a problem that arose from the shape of the Bessel beam. “It's not just a thin pencil of light – it has these dimmer side lobes,” Betzig explains. “So when you sweep that across a sample, you get out-of-focus light.” One solution was to shift the beam step-by-step across the sample, illuminating it with a grating pattern. The researchers could then computationally strip out the blurriness caused by the Bessel beam's side lobes – a technique known as structured illumination.

Structured illumination can also be used to overcome light microscopes' usual limits of spatial resolution. To apply a super-resolution structured illumination technique developed at Janelia by the late Mats Gustafsson, Betzig's team moved the Bessel beam to produce a lattice-like pattern of light. “With that we not only get rid of the side lobe stuff, we actually push the resolution a bit beyond the diffraction limit,” he says.

To reduce the time required to move the Bessel beam each time a sample was imaged, the developers split the beam into seven parallel parts, so each traveled just one-seventh of the original distance. Suddenly, the cells they were imaging seemed healthier. “What was shocking to us was that by spreading the energy out across seven beams instead of one, the phototoxicity went way down,” Betzig says. “What I learned from that experience is that while the total dose of light you put on the cell is important, what's far more important is the instantaneous power that you put on the cell.”

Could they reduce light toxicity even more by dividing the Bessel beam? Betzig wasn't sure what would happen when the beams began to crowd one another, so he modeled the potential effects. Although the beams interfered with one another, the model proposed certain arrangements where that interference actually destroyed the undesirable lobes of light. If he could reproduce those “magic periods” with actual light, the imaging potential was huge. “What you get is sort of a triple win,” he says. “You spread the energy out, this highly structured plane is ideal for doing structured illumination with high contrast, and you get rid of that nasty side lobe problem.”

That's when Betzig dusted off an idea he'd had more than 10 years ago. Working theoretically, he'd proposed a technique he called optical lattice microscopy, which would limit damage to cells by illuminating a sample with a massive three-dimensional array of light foci. Other technologies had taken hold when Betzig moved to Janelia in 2005, and he'd never built an optical lattice microscope. But the idea remained sound. “We used the lattice theory to predict the patterns that would produce these magic periods,” Betzig says.

"We know what the microscope can offer in terms of the imaging, but I think there are a lot of applications we haven't even thought of yet."

The new microscope operates in two modes. One uses the principles of structured illumination to create very high-resolution images. In this case, the final image is created by collecting and processing multiple images of every plane of the sample. Imaging can be sped up to capture faster processes, albeit at lower resolution, with an alternative “dithered” mode. Light exposure, and thus damage to cells, is lower in the dithered mode; in many cases, tagged proteins are naturally replaced by cells before their signal fades appreciably. “So there are many cells you could look at forever in 3D,” Betzig says.

Thirty teams of biologists have come to Janelia over the past year to find out what the lattice light sheet microscope can reveal about the systems they study. Chen, Legant, and Wang have worked with the researchers to optimize the technology for a variety of experiments. “This is not a single imaging technique,” Wang says. “It's an imaging platform.”

The Science paper includes videos of these and other processes gleaned from the Betzig team's collaborations, but the scientists say they represent only the beginning. “We know what the microscope can offer in terms of the imaging, but I think there are a lot of applications we haven't even thought of yet,” Legant says.

Betzig's team freely shares its designs, providing detailed instructions to scientists with the expertise to build their own version of the instrument. Zeiss has licensed the Bessel beam and lattice light sheet microscopy. “It takes a huge amount of effort to move from a successful high-tech prototype to broader adoption of an imaging technology,” Betzig says. “Ultimately, commercialization is the crucial last step to ensuring that these technologies can have broad impact in the research community.”



SOURCE  Howard Hughes Medical Institute

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 Microscopy  

By combining atomic force microscopy with infrared synchrotron light, researchers have improved the spatial resolution of infrared spectroscopy by orders of magnitude, while simultaneously covering its full spectroscopic range, enabling the investigation of variety of nanoscale, mesoscale, and surface phenomena that were previously difficult to study.

A new microscope has been developed that should allow researchers to study and identify molecules at the so-called mesoscale, a region of matter that ranges from 10 to 1000 nanometers in size. Using broadband infrared light from the Advanced Light Source (ALS) synchrotron at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), researchers have developed a broadband imaging technique that looks inside this realm with unprecedented sensitivity and range.

By combining atomic force microscopy with infrared synchrotron light, researchers from Berkeley Lab and the University of Colorado have improved the spatial resolution of infrared spectroscopy by orders of magnitude, while simultaneously covering its full spectroscopic range, enabling the investigation of variety of nanoscale, mesoscale, and surface phenomena that were previously difficult to study.

The new technique, called Synchrotron Infrared Nano-Spectroscopy or SINS, will enable in-depth study of complex molecular systems, including liquid batteries, living cells, novel electronic materials and stardust.

This peptoid nanosheet, produced by Gloria Olivier and Ron Zuckerman at Berkeley Lab, is less than 8 nanometers thick at points. SINS makes it possible to acquire spectroscopic images of these ultra-thin nanosheets for the first time. Image Source - Berkeley Lab

“The big thing is that we’re getting full broadband infrared spectroscopy at 100 to 1000 times smaller scale,” says Hans Bechtel, principal scientific engineering associate at Berkeley Lab. “This is not an incremental achievement. It’s really revolutionary.”

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In a Proceedings of the National Academy of Sciences paper published, “Ultra-broadband infrared nano-spectroscopic imaging,” Berkeley Lab’s Bechtel and Michael Martin, a Berkeley Lab staff scientist, and colleagues from Markus Raschke’s group at the University of Colorado at Boulder describe SINS. They demonstrate the nanoscope’s ability to capture broadband spectroscopic data over a variety of samples, including a semiconductor-insulator system, a mollusk shell, proteins, and a peptoid nanosheet. Martin says these demonstrations just “scratch the surface” of the potential of the new technique.

SINS combines two pre-existing infrared technologies: a newer technique called infrared scattering-scanning near-field optical microscopy (IR s-SNOM) and an old laboratory standby, known even to college chemistry students, called Fourier Transform Infrared Spectroscopy (FTIR). A clever melding of these two tools, combined with the intense infrared light of the synchrotron at Berkeley Lab gives the researchers the ability to identify clusters of molecules sized as small as 20 to 40 nanometers.

"The big thing is that we’re getting full broadband infrared spectroscopy at 100 to 1000 times smaller scale. This is not an incremental achievement. It’s really revolutionary."

The new approach overcomes long-standing barriers with pre-existing microscopy techniques that often involve demanding technical and sample preparation requirements. Infrared spectroscopy uses low-energy light, is minimally invasive, and is applicable under ambient conditions, making it an excellent tool for chemical and molecular identifications in systems that are static as well as those that are living and dynamic.

The technique works by shining low-energy infrared light onto a molecular sample. Molecules can be thought of as systems of balls (atoms) and springs (bonds between atoms) that vibrate with characteristic wiggles; they absorb infrared radiation at frequencies that correspond to their natural vibrating modes. The output from this absorption is a spectrum, often called a fingerprint, which shows distinctive peaks and dips, depending on the bonds and atoms present in the sample.

But infrared spectroscopy has its challenges too. While it works well for bulk samples, traditional infrared spectroscopy can’t resolve molecular composition below about 2000 nanometers. The major hurdle is the diffraction limit of light, which is the fundamental barrier that determines the smallest focus spot of light and is particularly troublesome for the large wavelengths of infrared light. In recent years, though, the diffraction limit has been overcome by a technique called scattering-scanning near-field optical microscopy, or s-SNOM, which involves shining light onto a metallic tip. The tip acts as an antenna for the light, directing it to a tiny region at its apex just tens of nanometers wide.

This trick is what’s used in IR s-SNOM, where infrared light is coupled to a metallic tip. The challenge with IR s-SNOM, however, is that researchers have been relying on infrared light produced by lasers. Lasers emit a large number of photons needed for the technique, but because they operate in a narrow wavelength band, they can only probe a narrow range of molecular vibrations. In other words, laser light simply can’t give you the flexibility to explore a spectrum of mixed molecules.

Bechtel, Martin and Raschke’s team saw the opportunity to use Berkeley Lab’s ALS to overcome the laser limitation. The lab’s synchrotron produces broadband infrared light with a high-photon count that can be focused to the diffraction limit. The researchers coupled the synchrotron light to a metallic tip with an apex of about 20 nanometers, focusing the infrared beam onto the samples. The resulting spectrum is analyzed with a modified FTIR instrument.

“This is actually one of very few examples where synchrotron light has been coupled to scanning probe microscopy,” says Raschke. “Moreover, the implementation of the technique at the synchrotron brings chemical nano-spectroscopy and -imaging out of the lab of a few laser science experts and makes it available for a broader scientific community at a user facility.”

The team demonstrated the technique by confirming the spectroscopic signature of silicon dioxide on silicon and by illustrating the sharp chemical transition that occurs within the shells of the blue mussel (M. edulis). Additionally, the researchers looked at proteins and a peptoid nanosheet, an engineered, ultra-thin film of proteins with medical and pharmacological applications.

Martin is excited for the potential of SINS, which is available for researchers from any institution to use. In particular he’s interested in a closer look at battery systems, with the hope that understanding battery chemistry on the mesoscale could provide insight into better performance. Further out, he expects SINS to be useful for a range of biochemistry as well. “This hints at a dream I’ve had in my mind, to look at the surface of a cell, inside the bi-layer membrane, the channels, and receptors,” says Martin. “If we could put a SINS tip on a living cell, we could watch biochemistry happen in real time.”

Bechtel, for his part, is intrigued by the possibility of using SINS for the study of lunar rocks, meteorites and stardust. These extraterrestrial materials have a molecular diversity that is difficult to resolve on the nanoscale, particularly in a non-destructive manner for these rare samples. A better understanding of the makeup of moon rocks and dust from space could provide clues to the formation of the planets and solar system.

Raschke is using the technique to study the processes that limit the performance of organic solar cells. He is looking to further improve the flexibility of the technique such that it can be applied under variable and controlled atmospheric and low-temperature conditions. Among other tweaks, he plans to increase the sensitivity of the technique with the ultimate goal of performing singe-molecule chemical spectroscopy.


SOURCE  Berkeley Lab

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 Microscopy  

A new technique, developed by researchers, provides a method to noninvasively measure human neural networks in order to characterize how they form.

By using spatial light interference microscopy (SLIM) techniques developed by Gabriel Popescu, director of the Quantitative Light Imaging Laboratory at the Beckman Institute, the researchers were able to show for the first time how human embryonic stem cell derived neurons within a network grow, organize spatially, and dynamically transport materials to one another.

“Because our method is label-free, we’ve imaged these type of neurons differentiating and maturing from neuron progenitor cells over 12 days without damage,” said Popescu. “I think this (technique) is pretty much the only way you can monitor for such a long time.”

Scientific Reports recently published their paper on the topic, “Label-Free Characterization of Emerging Human Neuronal Networks.”

"Many diseases result in subtle changes in how neural networks organize and behave, and now we have a tool to study these changes in a practical manner."

Using time-lapse measurement, the researchers are able to watch the changes over time. “We’ve been looking at the neurons every 10 minutes for 24 hours to see how the spatial organization and mass transport dynamics change,” said Taewoo Kim, one of the lead authors on the paper.

The SLIM technique measures the optical path length shift distribution, or the effective length of the path that light follows through the sample. “The light going through the neuron itself will be in a sense slower than the light going through the media around the neuron,” explains Kim. Accounting for that difference allows the researchers to see cell activity—how the cells are moving, forming neural clusters, and then connecting with other cells within the cluster or with other clusters of cells.

“Individual neurons act like they are getting on Facebook,” explains Popescu. “In our movies you can see how they extend these arms, these processes, and begin forming new connections, establishing a network.” Like many users of Facebook, once some connections have been made, the neurons divert attention from looking for more connections and begin to communicate with one another—exchanging materials and information. According to the researchers, the communication process begins after about 10 hours; for the first 10 hours the studies show that the main neuronal activity is dedicated to creating mass in the form of neural extensions or neurites, which allows them to extend their reach.

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“Since SLIM allows us to simultaneously measure several fundamental properties of these neural networks as they form, we were able to for the first time understand and characterize the link between changes that occur across a broad range of different spatial and temporal scales. This is impossible to do with any other existing technology,” explains Mustafa Mir, a lead author on the study.

The researchers used untreated cells and cells that were treated with lithium chloride, which delays neurite growth. This allowed them to compare the mass of both the treated and untreated cells, and showed that the main growth of cells is during the connection phase, where dendrites are being extended within and between clusters.

“When we first compared the data from the treated and untreated samples, the potential of this technique to answer important questions in neuroscience and developmental biology became clear. Many diseases result in subtle changes in how neural networks organize and behave, and now we have a tool to study these changes in a practical manner,” said Mir.

The work is done in conjunction with a science and technology center sponsored by the National Science Foundation, Emergent Behaviors of Integrated Cellular Systems (EBICS), which is a multi-institutional effort led by MIT, Georgia Tech, and the University of Illinois. The Illinois site is led by Rashid Bashir, from the Beckman 3D Micro- and Nanosystems Group and head of the Illinois Department of Bioengineering.

EBICS is examining the way that complex systems and patterns rise out of relatively simple interactions with a goal of building living, multi-cellular machines that solve real-world problems in health, security, and the environment.

“Through this center in the past four years, we’ve developed a number of tools trying to understand emergence, trying to define what emergence means,” said Popescu. “This paper is a clear example of our progress toward defining and quantifying this important and universal phenomena.

“We developed these methods based on SLIM to understand at what scale the cells get organized, they become predictable. We quantify emergence versus spatial and temporal scales at which order occurs. The formation of a neuron network is a beautiful example of how emergence occurs. You deploy the cells that have nothing to do with one another—they are completely independent. Then, in less than 24 hours they start to talk to one another—operate more as an ensemble, an organized group, rather than as individuals. Using SLIM we can attest that, although structurally, individual cells do not change much over short time scales, it is their arrangement in space and their collective behavior in time that evolves quickly.”

Popescu hopes that his work will help in building machines that can help with health-related questions, including Alzheimer’s, memory-related conditions, and aging. The first step is to identify the deterministic behavior of the neural cells and discover treatments that enhance this predictable behavior.

"Although in this study we have used SLIM to examine neural networks, the technology showcased here can be applied to a wide variety of biological systems, this is only the tip of the iceberg."

“I think we have a set of good tools to both structurally and dynamically tell the difference when cells are functioning in various modes now. The plan is to control the predictable part, such as material transport in neurons or beating in heart cells, and hopefully get the cells to accomplish small tasks,” said Popescu.

“Although in this study we have used SLIM to examine neural networks, the technology showcased here can be applied to a wide variety of biological systems, this is only the tip of the iceberg,” said Mir.

“SLIM technology holds tremendous promise for imaging not only cell-based networks, but also whole slices of brain tissue, where the connections laid down during development are preserved and natural functionalities are expressed,” said Martha Gillette, a neuroscientist in the Neurotech Group at the Beckman Institute and collaborator on the study. “Heterogeneities among individual cells of functionally specialized brain regions are emerging as key contributors to healthy versus diseased states. The ability to analyze individual cells within a multicellular micro-environment that preserves the native structural and functional complexity of the brain is a major challenge that can be addressed using SLIM.”




SOURCE  Beckman Institute

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 Cell Biology  

Researchers have deciphered the structure of part of the ribosome found in mitochondria, the power plants of the cell. The scientists were able to benefit from advancements in the field of electron microscopy and capture images of the mitochondrial ribosome at a level of resolution never achieved before.

The ribosome can be thought of as a decryption device housed within the cell. It is able to decipher the genetic code, which is delivered in the form of messenger ribonucleic acid (mRNA), and translate it into a specific sequence of amino acids. The final assembly of amino acids into long protein chains also takes place in these enzyme complexes. Without ribosomes, a cell would be unable to produce any proteins. Due to their central function, these enzyme complexes have long been the focus of attention of biologists.

In order to obtain a better understanding of ribosomes, which are found in all cells, it is imperative to know their exact composition and structure.

Over the past 15 years, Nenad Ban, professor at ETH Zurich, has made a significant contribution to not only the elucidation of the ribosome structure of bacteria, but also of higher organisms, termed eukaryotes, which include fungi, plants and animals.

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Until now, the molecular structure of the ribosomes found in mitochondria, the power plants of the cell, was still largely unknown. Mitochondrial ribosomes differ considerably from the ‘ordinary’ ribosomes found in the cytoplasm, which are composed of 60% ribonucleic acids (RNA) and 40% protein components.

In the case of mitochondrial ribosomes, RNA accounts for just under a third of the entire complex. One reason for this is that the RNA molecules have shortened significantly over the course of evolutionary history. Mitochondrial ribosomes in the cell are primarily localised at the inner membrane of mitochondria and are present within the cell in a far smaller number than the cytoplasmic ribosomes. This makes them more difficult to isolate, hampering progress of research in the field.

A team of researchers from the ETH research groups of Ban and Ruedi Aebersold have now succeeded in elucidating the structure of the large subunit of the mitochondrial ribosomes from mammalian cells to a resolution of 4.9 angstroms (less than 0.5 nanometres). Such a level of resolution allows, for example, the visualization of individual phosphate groups of the ribosomal RNA. The researchers’ findings were published in Nature as the cover story.

Image Source - Ban et al, Nature

The ETH researchers used the latest generation of high-resolution cryo-electron microscopes, which have only recently become available. The researchers captured more than a million images of the large subunit of the mitoribosome and reconstructed its three-dimensional structure by performing complex calculations on a computer cluster.

In order to interpret the calculated structure as precisely as possible and to determine the exact location of the RNA and protein molecules within the enzyme complex, the researchers used a method derived from Aebersold’s laboratory – a method called ‘chemical cross-linking combined with mass spectrometry.’ Here, the individual protein components of the ribosome are chemically cross-linked, fragmented into peptides for further analysis, and sequenced in the mass spectrometer.

From this data, it is then possible to determine the structure of a protein complex, such as the ribosome and its large subunit. A great deal of computer power is required, however, and so the research team used Brutus, ETH’s high-performance cluster.

The combination of these methods enabled the researchers to succeed in creating a high-resolution structural model of the large subunit of the mitochondrial ribosome with unprecedented precision.

Thanks to their new findings, the researchers can now explain why mitochondrial ribosomes are always located at the membrane of the mitochondrion. In the vicinity of the tunnel exit, through which freshly synthesised proteins leave the ribosome, the biologists were able to localise a protein with similarity to membrane anchor proteins. From this observation, they have been able to conclude that during the course of evolution an anchor protein of this kind was integrated in the ribosome in order to fix it to the mitochondrial membrane, thus allowing the freshly synthesised proteins to be targeted directly to their destination in the membrane.

On the basis of this ground-breaking work, the researchers also hope to gain new insights into the functioning and disorders of this important cellular organelle. Defects in the genetic material coding for the components of mitochondria can lead, for example, to muscle diseases and also play a role in cancer.

Cancer cells not only require high levels of nutrients in order to grow quickly, but also large amounts of energy. Their energy metabolism therefore is in an unusual state, to which the mitochondria probably also contribute. Ban makes clear, however, that no application-related questions are currently being addressed. “The structure of this ribosome provides an important foundation on which other researchers can build,” he says.



SOURCE  ETH Zurich

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 Apps  

Eowyn Applegate shares six apps for the amateur and budding scientist alike, including The Night Sky and Leafsnap among others.

Remember when you were a kid and amazed by everything around you? A spiral rock, the stars above, the elephants at the zoo all inspired you? Thanks to app developers covering every branch of natural science, you can let your inner child soar as you explore and learn with some of these incredible apps.

1. Leafsnap (free)

Have you ever wondered about the beauty around you? Leafsnap will help you recognize, learn, and appreciate nature. Pick up a fallen leaf, snap a picture, and Leafsnap will identify it for you. Next time you go on a nature walk, you can leave the guidebook at home!

2. TouchSurgery (free)

Not for the squeamish, this app is a surgical simulator that allows you to learn surgeries through interactive training. Created by surgeons, it was designed so trainees could get some safe practice and build confidence. Even if you aren't planning to be a surgeon yourself, you'll be amazed by what you learn about human anatomy.

3. The Night Sky ($0.99)

THE stargazing app, The Night Sky 2 allows you to see what stars are in front of you by simply holding up your phone or tablet. Find out if those clouds will part, and check out the sunrise time on a certain day to make sure you don't miss a comet viewing.

4. Smart Microscope ($3.99)

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Ever wanted to know what a bed bug looked like up close? With Smart Microscope, you can download over 70 slides of insects, plants, medical specimens of humans, and more. You can zoom in and out of the slide and read what the experts have to say about what you're seeing.

For the serious micro-gazer, check out http://www.microscope.com/ and grab their microscope camera for your iPad. Share the single view of the microscope with everyone around you. 

5. The Incomplete Map for the Cosmic Genome ($8.99)

This is an invaluable app for anyone who wants to learn and keep up-to-date on what the great scientific minds of today are doing. Watch and listen to interviews and videos that cover all the sciences, and keep coming back for new ideas, theories, and discussions.

6. The Elements: A Visual Exploration ($13.99)

Tired of seeing the periodic table and looking away before you learn anything? You will want this app and a lot more time, because it is addictive. Diving deeper than just the table, you can see (with brilliant imagery) all the details and information of an element.

So, find what you love, let out your inner child, and be amazed by the world around you all over again. As an adult, you'll be able to appreciate it more than ever.

By Eowyn Applegates

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 Neuroscience  

Researchers in Vienna develop new imaging technique to study the function of entire nervous systems The scientists have found a way to overcome some of the limitations of light microscopy. Applying the new technique, they can record the activity of a worm’s brain with high temporal and spatial resolution, ultimately linking brain anatomy to brain function.

Researchers at the Campus Vienna Biocenter in Austria have found a way to overcome some of the limitations of light microscopy. Applying anew technique, they can record the activity of a worm’s brain with high temporal and spatial resolution, ultimately linking brain anatomy to brain function.

The research has been published in the journal Nature Methods.

A major aim of today’s neuroscience is to understand how an organism’s nervous system processes sensory input and generates behavior. To achieve this goal, scientists must obtain detailed maps of how the nerve cells are wired up in the brain, as well as information on how these networks interact in real time.

The organism many neuroscientists turn to in order to study brain function is a tiny, transparent worm found in rotting soil. The simple nematode C. elegans is equipped with just 302 neurons that are connected by roughly 8000 synapses. It is the only animal for which a complete nervous system, or connectome, has been anatomically mapped.

Researchers have so far focused on studying the activity of single neurons and small networks in the worm, but have not been able to establish a functional map of the entire nervous system. This is mainly due to limitations in the imaging-techniques they employ: the activity of single cells can be resolved with high precision, but simultaneously looking at the function of all neurons that comprise entire brains has been a major challenge. Thus, there was always a trade-off between spatial or temporal accuracy and the size of brain regions that could be studied.

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Now scientists at Vienna’s Research Institute of Molecular Pathology (IMP), the Max Perutz Laboratories (MFPL), and the Research Platform Quantum Phenomena & Nanoscale Biological Systems (QuNaBioS) of the University of Vienna have closed this gap and developed a high speed imaging technique with single neuron resolution that bypasses these limitations.

The teams of Alipasha Vaziri and Manuel Zimmer describe the technique which is based on their ability to “sculpt” the three-dimensional distribution of light in the sample. With this new kind of microscopy, they are able to record the activity of 70% of the nerve cells in a worm’s head with high spatial and temporal resolution.

“Previously, we would have to scan the focused light by the microscope in all three dimensions”, says quantum physicist Robert Prevedel. “That takes far too long to record the activity of all neurons at the same time. The trick we invented tinkers with the light waves in a way that allows us to generate “discs” of light in the sample. Therefore, we only have to scan in one dimension to get the information we need. We end up with three-dimensional videos that show the simultaneous activities of a large number of neurons and how they change over time.”

Prevedel is a Senior Postdoc in the lab of Alipasha Vaziri, who is an IMP-MFPL Group Leader and is heading the Research Platform Quantum Phenomena & Nanoscale Biological Systems (QuNaBioS) of the University of Vienna, where the new technique was developed.

The new microscopic method is only half the story. Visualization of the neurons requires tagging them with a fluorescent protein that lights up when it binds to calcium, signaling the nerve cells’ activity.

“The neurons in a worm’s head are so densely packed that we could not distinguish them on our first images”, explains neurobiologist Tina Schrödel, co-first author of the study. “Our solution was to insert the calcium sensor into the nuclei rather than the entire cells, thereby sharpening the image so we could identify single neurons.” Schrödel is a Doctoral Student in the lab of the IMP Group Leader Manuel Zimmer.

The new technique that came about by a close collaboration of physicists and neurobiologists has great potentials beyond studies in worms, according to the researchers. It will open up the way for experiments that were not possible before. One of the questions that will be addressed is how the brain processes sensory information to “plan” specific movements and then executes them.

This ambitious project will require further refinement of both the microscopy methods and computational methods in order to study freely moving animals. The team in Vienna is set to achieve this goal in the coming two years.



SOURCE  University of Vienna

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