The Magazine of Forschungszentrum J端lich
RESEARCH in J端lich
:: Sights Set on Safety J端lich Researchers Work on Solutions for Nuclear Waste Management :: In Close Contact: How Cells Take Up Nanoparticles :: Exhibition in Ghent: Art from a Supercomputer
02|2014
:: IN THE PICTURE “It never gets boring around here!” Glassware maker Patrick Pistel and his colleagues at Jülich’s Central Institute of Engineering, Electronics and Analytics fabricate customized glassware – from flasks to kerosene reformers. The only thing the intricate objects have in common is that there is nothing quite like them on the market. Otherwise they are all one-of-a-kind – designed, developed, and fabricated for the specific questions addressed by Jülich researchers. The result: “visionary solutions”, as the glassware makers themselves dub their custom-made products.
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CONTENTS
:: NEWS IN BRIEF
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:: COVER STORY
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6 Safety for Future Generations Research on the final disposal of radioactive waste 9 The Effects of Water Understanding the processes in a final repository
:: RESEARCH AT THE CENTRE
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12 Inspiration from the Supermarket Neuroscience uses statistical method from retailing market research 14 Up Close and Personal on the Nanoscale How cells let nanoparticles in 16 Nanomedicine: Somewhere Between Hype and Hope Interview with Munich professor Wolfgang M. Heckl 17 Something in the Air over Spa Town? Climate researchers measure air quality in Bad Homburg 18 Glow of Satisfaction as Dream Comes True Excellent business model: sorting facility for bacteria 20 Gold Mine in the Cowshed Manure as a raw material for customized fertilizers
:: LAST BUT NOT LEAST
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22 Art from a Supercomputer Unusual computing task for JUROPA 23 Publication Details
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:: Editorial Even though nobody wants it, it’s there, and we cannot simply leave it to take care of itself: high-level radioactive waste from our nuclear power plants, which will continue to emit radiation for thousands of years to come. We need to find a solution for its final disposal in order to protect future generations in the best possible way. Forschungszentrum Jülich, with its expertise in waste management research, considers it a special duty to make a contribution to these efforts. Jülich experts analyse the behaviour of radioactive waste under different final disposal conditions right down to the level of atoms and molecules, thus helping to find the safest solution. You will also discover what brain researchers have to do with supermarkets and why cells love to be in close contact. I hope that this issue makes for interesting reading! Yours sincerely, Prof. Achim Bachem Chairman of the Board of Directors of Forschungszentrum Jülich
Just Like Paradise Jülich Supercomputing Centre | Male birds-of-paradise impress females with the iridescence of their feathers. Researchers from Jülich and Groningen in the Netherlands have now succeeded in simulating the complex optical properties of their plumage on a computer. The computer model developed for this purpose could also help to produce nanostructured materials with special optical properties. ::
Sharp Images of Thicker Samples Peter Grünberg Institute | 3D cryoelectron microscopy provides researchers with important insights into the cell structure of biological samples. As in computer tomography, the method creates a three-dimensional image from a large number of two-dimensional pictures. Scientists from the Ernst RuskaCentre – a cooperation between Forschungszentrum Jülich and RWTH Aachen University – and from the Weiz-
mann Institute of Science in Israel have applied scanning transmission electron microscopy, a well-established method in materials research, to biological samples. Compared with conventional phase-contrast methods, this procedure makes it possible to record high-resolution images of thicker samples, such as bacteria. It thus widens the range of options for 3D cryo-electron microscopy. ::
3D image of Agrobacterium tumefaciens soil bacteria
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Research in Jülich 2 | 2014
News in Brief
Crowding in Blood Vessels Simulated Institute of Complex Systems/Institute for Advanced Simulation | White blood cells serve as the police force of the body’s immune system. They drift through arteries and veins with the blood. If necessary, they penetrate the walls of arteria to fight intruders such as viruses. Since they do not move actively in the blood stream, it was until recently unclear how they reach the walls of the blood vessels. Jülich researchers have now been the first to examine the process in detail using three-dimensional computer simulations. An average number of red blood cells and a low flow velocity will push a white blood cell towards the wall of the blood vessel (a). It can then pass through the vessel wall. However, if the number of red blood cells is low and the flow velocity high, the white blood cell will continue to go with the particle flow and cannot reach the vessel wall (b). The simulation could also be helpful in developing new techniques for diagnosing illnesses. :: a) Pushed to the edge or …
b) … right in the middle of the particle stream
Speed Matters Peter Grünberg Institute | Spin electronics is considered a promising basis for faster and more energy-efficient future data processing. Researchers from Jülich, Strasbourg, and Shanghai have discovered an effect that produces spin waves with defined frequencies with much greater ease than was previously thought possible. Their computer simulations demonstrate that such waves form when a magnetic field pulse passes alongside a magnetic material at sufficient velocity. The scientists were even able to control the frequency of the spin waves by influencing the speed at which the field pulse moves. Targeted control is important for spin waves to be utilized for technical purposes. The researchers have named the new phenomenon the “Spin-Cherenkov effect” based on the Cherenkov effect, which occurs when charged particles pass through water faster than the phase velocity of light. ::
Vapours Cause Growth Spurt Institute of Energy and Climate Research | A hundred nanometres is quite sufficient a size for an aerosol particle in the air to have an impact on climate – for example by acting as a condensation nucleus for cloud formation or by reflecting incident sunlight back into the atmosphere. Scientists have long puzzled over the exact processes in which these suspended particles form. An international team of researchers headed by Thomas Mentel from Jülich have now reported in the scientific journal Nature that certain vapours in the atmosphere cause aerosol particles to grow. Supported by numerous experiments, the scientists have been able to clarify how these vapours form almost immediately when trees and other plants release certain substances into the atmosphere. ::
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Certain vapours in the atmosphere make aerosols grow so large that they have an impact on climate.
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What spurs me on is that I don’t just work with model substances, but with the very material that will eventually be sent to a final repository. Dr. Hildegard Curtius Research in Jülich 2 | 2014
COVER STORY | Waste Management Research
Safety for Future Generations “It’s an issue we don’t want our children to have to deal with,” is how Prof. Dirk Bosbach sums up his mission in the field of nuclear waste management research. The Jülich scientist and his team are working on the fundamentals of safely storing radioactive waste.
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y the end of 2011, German nuclear power plants had already left a legacy of 7,790 tonnes of spent nuclear fuel rods. It will take hundreds of thousands of years until their radioactive decay is more or less complete. The German Office for Radiation Protection estimates that another 2,760 tonnes will be added before the last German nuclear power plant stops producing electricity in 2022. Together with storage containers and the high-level radioactive waste that Germany has to take back from the reprocessing plants in France and the United Kingdom, the spent nuclear fuel rods will have a total volume of around 28,100 m3. This corresponds roughly to the volume of ten Olympic-size swimming pools. The long-term radioactivity is emitted by substances that make up less than 1 % of the spent fuel elements. But how can high-level radioactive waste be disposed of safely? Almost all experts agree that it would be best to store the radioactive waste several hundred metres below the surface of the Earth in suitable rock formations – an option that was first proposed as early as the 1960s. The rock naturally prevents radioactivity from being released into the biosphere. In addition, containers, filling materials, and other technical barriers will also protect the material. The search for the best site and concept for such a final repository, and the associated risk analyses, raise questions regarding geology, engineering, nuclear chemistry, and physics that can only be answered by means of research. In Germany, the related research tasks have
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been assigned to different public institutions. For example, the Federal Institute for Geosciences and Natural Resources is responsible for geological research. The Helmholtz Association, of which Forschungszentrum Jülich is a member, investigates the behaviour of different types of radioactive atoms – or radionuclides, as the experts say – under different conditions. 50 YEARS OF RESEARCH As a former nuclear research centre, Jülich has been pursuing nuclear waste management research for the last 50 years. However, the framework conditions have changed substantially during this time: In the early years, buoyed by great enthusiasm for the new technology, researchers worked on the use of nuclear energy with a closed fuel cycle, including a reprocessing step. “Today, in contrast, after the federal government decided to phase out nuclear power in Germany and Jülich’s DIDO research reactor was decommissioned in 2006, our research helps us to meet long-term responsibilities for the disposal of nuclear fuels, for example from the reactors that used to be operated at Jülich,” says Prof. Dirk Bosbach, who heads Nuclear Waste Management at the Institute of Energy and Climate Research. What he means by long-term responsibilities: “The behaviour of the radioactive waste in a final repository must be projected hundreds of thousands of years into the future,” says Bosbach. In order to look this far ahead, scientists usually employ the scenario method: ex-
Prof. Dirk Bosbach is a director at the Institute of Energy and Climate Research and lectures at RWTH Aachen University.
perts devise a range of scenarios – possible future developments – that is so comprehensive that it includes the actual future development. “For each individual scenario, it must then be demonstrated that the final repository is safe,” says Bosbach’s colleague Dr. Guido Deissmann. For a final repository in a rock formation deep underground, one scenario is that radioactive waste comes into contact with water. “We use ex periments, simulation results, and thermodynamic calculations to determine the processes that would occur in a final repository in such a case,” says Bosbach.
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Final repository with a multi-barrier system
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This concept envisages that the radioactive waste will be stored at a depth of several hundred metres. Various barriers shield the waste from the environment completely. All of these (geo)technical barriers are intended to compensate for the weaknesses of the natural barriers. The aim is to prevent the radioactive waste from coming into direct contact with the biosphere. Natural barriers 1 Environment 2 Geosphere 3 Host rock
Geotechnical barriers 4 Seals 5 Backfill material
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Technical barriers 6 Container
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7 Waste form
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WINDOWS 50 CM THICK Jülich has a comprehensive infrastructure for collecting experimental data. For example, so-called “hot cells” were introduced at Forschungszentrum Jülich in the 1970s. These are laboratory areas with radiation protection windows 50 cm thick and shielded with special walls. Here, highly radioactive material – the material that will eventually be stored in a final repository – can be examined using telemanipulators. The only other hot cells in Germany are located at Karlsruhe. The Jülich hot cell facility is also used by fusion researchers and for reactor dismantling. In addition, the researchers headed by Bosbach also benefit from the know-how and devices used by other disciplines at Forschungszentrum Jülich.
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They work particularly closely with electron microscopy experts at the Ernst Ruska-Centre, theoretical physicists at the Peter Grünberg Institute, and with the Jülich Supercomputing Centre. “Cooperation helps us to understand the behaviour of radioactive waste under the conditions in a final repository right down to the level of atoms and molecules – which is a prerequisite for making reliable forecasts regarding longterm safety,” says Bosbach. Such forecasts will play a decisive role in the selection of a site for a permanent nuclear repository in Germany. The law stipulates that this process should be completed by 2031. “The waste management concept requires the interim storage of the high-level radioac-
tive waste for a period of 30 to 40 years,” says Bosbach. Numerous radionuclides in the waste become stable nuclides after a relatively short period of time. Radioactivity and the associated heat generation in the nuclear waste thus drop particularly quickly during the first few decades, so that after this period, it becomes easier to build a final repository that meets the requirements for heat removal and the safe confinement of the waste. :: Frank Frick
Research in Jülich 2 | 2014
COVER STORY | Waste Management Research
The Effects of Water
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woman’s voice is giving instructions, such as “move closer” or “check position of hands”. Dr. Hildegard Curtius is familiar with the procedure. She calmly follows the instructions and positions herself correctly in a space the size of a shower cubicle: the tip of her nose almost touching the metal wall, her hands raised to her left and right, and her feet standing on wire grating. While the voice counts down from ten to zero, Curtius’ body is scanned to detect any ionizing radiation. Then the sliding glass door opens and Curtius can leave the cubicle. The measurements are prescribed by law and are routinely performed every time someone leaves the “hot cells”. These are specially shielded laboratories in which experiments can be carried out on highly radioactive substances using gripper arms referred to as manipulators. Only in these laboratories can Jülich researchers handle real waste from nuclear reactors – a prerequisite for examining the behaviour of these substances in a final repository. Hildegard Curtius has been working at Forschungszentrum Jülich for 18 years. She studies the behaviour of spent nuclear fuels. “What spurs me on is that I don’t just work with model substances, but with the very material that will eventually be sent to a final repository,” she says. She studies one of the greatest risks associated with a final repository, namely what would happen if the spent fuel came into contact with water. For example, Curtius discovered that water corrodes spent fuel elements from research reactors much faster than those from reactors for power generation. The composition of research reactor fuel elements is different because they are intended to emit as many neutrons – electrically neutral nuclear particles – as pos-
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sible during operation. After only a few years of contact with water, these fuel elements lose their shape and form a mud-like residue. At first sight, this doesn’t bode well for safety because it means that the radionuclides – radioactive atoms – could reach the water particularly quickly. However: “Almost all corrosion products in the mud-like residue bind to, or absorb, the radioactive atoms that are initially released, so that they cannot spread any further,” summarizes Curtius. The next task is to understand these processes in detail in order
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to reliably assess long-term safety in the scenario of contact with water. An entirely different phenomenon also involving water in direct contact with radioactive waste is being investigated by Dr. Felix Brandt and PhD student Juliane Weber from the Institute of Energy and Climate Research – Nuclear Waste Management and Reactor Safety (IEK6). After about 100,000 years, spent fuel elements form relatively large amounts of radium as a result of the radioactive decay of uranium-238. In principle, radium dissolves well in water
The materials we study here serve as catalysts in chemistry – it’s fascinating to me to look at another side of these materials. Yulia Arinicheva
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It’s incredibly exciting to analyse materials with a variety of methods and to cooperate with scientists from diverse backgrounds and disciplines. Sarah Finkeldei
and doesn’t bind strongly to the minerals that may be used as a barrier in a final repository. So far, this process has not played a major role in safety considerations, because it will only become significant in the distant future. Nevertheless, for the actual construction of a final repository, such processes need to be taken into account. This is one of the reasons why Svensk Kärnbränslehantering (SKB), the company that is planning to build a final repository in
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Sweden, is providing funding for Weber’s PhD thesis. RESPONSIBLE RESEARCH Weber is examining a process in a final repository that may reduce the amount of radium that could end up in the water and thus be transported out of the repository: the reaction of radium with barium, which also arises from the radioactive waste, and with sulfate, which occurs naturally. These three components
together form solid mixed crystals. Based on Weber’s experiments combined with atomistic simulations and thermodynamic calculations, the researchers headed by Brandt have demonstrated the extent to which mixed crystals are formed. SKB needs these figures for the safety analyses the company is required to submit to the authorities. Weber comments: “For me, it’s important to work on a topic that is of relevance for society.”
Research in Jülich 2 | 2014
COVER STORY | Waste Management Research
NATURAL RADIATION PROTECTION PhD student Yulia Arinicheva, in contrast, is motivated primarily by scientific curiosity. She and her colleague Sarah Finkeldei are studying the possibility of integrating long-lived radionuclides from nuclear waste into ceramic materials. Disposing of the waste in this form could reduce the probability of radioactivity from the final repository being released into the biosphere. Such ceramics are chemically very stable under the influence of water, high temperatures, and ionizing radiation. This is demonstrated by the natural relatives of these ceramics: monazites, phosphate minerals that contain up to 30 % radioactive thorium and uranium. They do not exhibit any radiation damage, although some of them have been around for billions of years. Arinicheva and Finkeldei therefore produce ceramics in the laboratory in order to study their properties in detail. “In Germany, the law stipulates that high-level radioactive waste should be disposed of directly, without integrating it into ceramics,” says Prof. Dirk Bosbach, director at IEK-6. “However, as scientists, we want to see what’s possible and explore options that may be particularly safe and advantageous.” Arinicheva wrote her master’s dissertation on “green chemistry”, namely the conversion of biomass using catalysts. “The materials we study here serve as catalysts in those processes – it’s fascinating to me to look at another side of these materials now,” says Arinicheva. She also knows how to share this fascination with others: with a short and entertaining presentation on her work, she won the science slam at the end of March at Kulturbahnhof Jülich – a competition where scientists present their own work to a diverse audience. Her colleague Sarah Finkeldei particularly likes the varied, interdisciplinary, and international environment at Nuclear Waste Management: “It’s incredibly exciting to analyse materials with a variety of state-of-the-art methods and to cooperate with scientists from diverse backgrounds and disciplines in order to find out how the results, all of which constitute pieces of a large puzzle, fit together and contribute to a fundamental understanding.”
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Using supercomputers, Dr. Piotr Kowalski is solving the riddle of the structure of radioactive materials.
SUPERCALCULATIONS Two researchers who have been particularly helpful to Finkeldei are Dr. Piotr Kowalski, head of the Jülich young investigators group “Atomistic Modeling” at IEK-6, and PhD student George Beridze. They use supercomputers to calculate the structural arrangement of radionuclides – mostly actinoids – in Finkeldei’s pyrochlore ceramics and in other materials based on their quantum chemical properties. “Jülich enjoys international renown not only for its expertise in materials research, but also its supercomputers and the associated know-how – and we benefit from both,” says Kowalski. His colleague George Beridze is motivated by the fact that Jülich is a leading institution and the knowledge that his theoretical model calculations are important for experimenters and also for practical considerations. The two scientists’ calculations are extremely sophisticated. All of the actinoids have a particularly large number of electrons that have a strong impact on each other, and all of these interactions need to be taken into account in their calculations. “We’re proud that our calculations are very reliable despite the
fact that they are so complicated,” says Kowalski. It is not surprising that, as a theoretician, he doesn’t work in the hot cells. However, neither do Juliane Weber, Yulia Arinicheva, and Sarah Finkeldei perform their experiments in hot cells behind 50 cm of lead glass. They work in a radiation protection area similar to those found in radiological laboratories in hospitals. The main reason for this is that in their experiments, the researchers use the tiniest amounts of these substances, so that at most they are only slightly radioactive. However, this is sufficient to gain fundamental findings on the technical aspects of final disposal. :: Frank Frick
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Inspiration from the Supermarket Neuroscientist Sonja Grün uses methods from retailing market research to understand how neurons cooperate.
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ave you ever wanted to know how long a glance lasts in scientific terms? And what happens in the process? Take a quick look at this photo:
The eye doesn’t take long to identify the mosquito. Your gaze scans the contours, rests on a point near the end of the wing – scientists call this “fixation” – and then abruptly moves to another point, such as the eye. Scientists refer to this movement as a saccade. The eye requires a total of 250 milliseconds, or a quarter of a second, to register the visual information, process it, and prepare for another eye movement to a new point of fixation. That’s how long a glance lasts. For the brain, this rapid perception of an object is a trivial task. It performs this action thousands of times a day, leaving us free to concentrate on other thoughts. For brain researchers, however, it is a mystery. How do we perceive things? How do our neurons process signals from the eye? Which cells communicate with each other, and in what way? And how do they decide in a matter of milliseconds where our gaze should go? It is questions like these that interest Prof. Sonja Grün from the Institute of Neuroscience and Medicine (INM-6). She investigates what happens in the brain during a glance – and has shown that neurons form teams in order to co-
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ordinate the processes that occur, such as fixation or saccades. The professor set out to discover which neurons are active simultaneously, and at which times. When evaluating the data, she made use of a helpful algorithm that is also applied in retailing market research. The analogy with retailing market research struck Sonja Grün for the first time during a spring school held by the Interdisciplinary College at the Möhne Reservoir. She was listening to a presentation by a computer scientist on intelligent data mining in retailing market research. Retailing market researchers want to find out how products should be placed in supermarkets so as to increase sales. If someone buys charcoal and sausages, for instance – wouldn’t they be more likely to pick up a bottle of barbecue sauce, too, if it was right beside the charcoal? To identify product groups like the “barbecue group”, the researchers analyse the contents of shopping trolleys. In doing so, however, they are confronted with a statistical problem: while charcoal, sausages, and sauce obviously belong together, the presence of mustard and chocolate in one trolley is more likely to be a random occurrence. But how can you tell the difference? Random or systematic? At this point, Sonja Grün pricked up her ears. She had a similar question, even though it concerned an entirely different field – brain research. She wanted to identify and analyse the activity patterns of neurons. Which concurrencies are random, and which point to a group of neurons that fire in unison, thereby triggering another process – such as an eye movement, perhaps?
Physicist Prof. Sonja Grün uses statistical methods to explain how neurons organize themselves in the brain.
Retailing market researchers, explained the computer scientist, solve such problems by means of frequent itemset mining (FIM). This method detects groups of objects in large data volumes quickly and efficiently, counts their frequencies, and sorts them according to various criteria, such as the probability of a pattern – for example, products often purchased together. FIM helps large online retailers to generate product suggestions that can be astonishingly accurate. Sonja Grün realized that this technique could also be used to identify functional groups of neurons. The professor promptly approached the computer scientist, and from a lengthy, animated conversation grew a successful exchange between two very different disciplines. “In the course of several years’ work, we supplemented the statistical methods of retailing market research, transferred them to brain research, and have
Research in Jülich 2 | 2014
RESEARCH AT THE CENTRE | Brain Research
now applied them to existing data,” explains Sonja Grün. Experiments had provided detailed measurements of the activity of up to 100 individual neurons while an animal gazed at objects for several moments. “Normally, a small number of neurons are always active at any given millisecond. However, during certain actions, such as fixating on an object, a much larger number of neurons suddenly become active at the same time. To distinguish behaviour-dependent activity patterns from random patterns, we supplemented the FIM method with a statistical method. Using the modified FIM, we were able to establish which of the simultaneously active neu-
tion to that faced in physics before the discovery of quantum theory: despite having increasing amounts of increasingly accurate data, we lack an all-encompassing theory for interpreting those data,” says Sonja Grün. In her search for such a theory, the professor will continue to look beyond the boundaries of her discipline. ::
rons form a functional group, for instance while the gaze is directed at a given object,” explains Sonja Grün. The professor has thus come closer than any other researcher to understanding gaze in the brain. Mystery still unsolved As yet, however, the mystery remains unsolved. Why do the neuron groups form, and how are they disbanded? Do they interact with other teams? And could a thought be a group of signals travelling through the brain? Satisfactory answers to these questions have not yet been found. “In neuroscience, we’re in a similar situa-
Christoph Mann
Shopping behaviour and neuron activity
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Neurons
The statistical method known as “frequent itemset mining” (FIM) finds groups of objects in large volumes of data quickly and efficiently and counts their frequencies. In retailing market research, this is used, for example, to identify products that are often purchased together. In brain research, a modified version of the FIM method helps to distinguish behaviour-dependent activity patterns from random patterns. This enabled Jülich scientists to establish which of the simultaneously active neurons form a functional group, for instance while the eye focuses on a given object.
Time in seconds
Time 1 2 3 4 5 6
Random combinations Same combination, thus a high probability that it is not random
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Random simultaneous activity Same group of neurons active simultaneously
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Up Close and Personal on the Nanoscale Cells are charming. They cosy up to large molecules or tiny nanoparticles that attach themselves to their outer wall. When letting them into their interior, cells have certain preferences, as Jülich researchers recently discovered.
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he more physical contact, the better: by means of computer simulations, Jülich researchers have demonstrated that the shape of a particle docking on to a cell influences its uptake by that cell. Using an innovative computing model, they tested whether and how cubic, spherical, or cylindrical particles are absorbed. The findings will help to selectively develop nanopharmaceuticals that are implanted into certain
Outlook for the future: tiny particles of active substances penetrate the cell membrane and fight diseases such as cancer or Crohn’s disease directly at their place of origin.
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Nanoparticles have a diameter around
10,000 times smaller than a human hair
cells, where they release active substances to fight diseases such as cancer, diabetes, or Crohn’s disease. Cells love close contact. Physically, therefore, the particle and the cell membrane want to achieve as large a contact area as possible. Because only when there is sufficient mechanical binding between the membrane and the particle – known as adhesion strength – can the elasticity of the cell membrane be overcome and the particle can penetrate into the interior of the cell. Relation with corners and edges “Our computerized model calculations show that the membrane can wrap around the particles either continuously or in stages,” says Prof. Gerhard Gompper, director at the Institute of Complex Systems of Forschungszentrum Jülich. The sides of a cube, for instance, adhere to the cell membrane easily, as this requires hardly any membrane deformation. In the next stage, however, the membrane must position itself over the cube’s edges at a 90-degree angle. The high level of membrane deformation costs the cell a great deal of energy. In the case of a spherical particle, in contrast, the membrane wraps itself around the particle continuously, always requiring the same amount of energy per unit area, as the particle has the same curvature at every point. To do so, the force of attraction must simply be greater than the stiffness of the membrane. For cubes, cuboids, and ellipsoids, the Jülich researchers systematically investigated the influence of edge curva-
Research in Jülich 2 | 2014
RESEARCH AT THE CENTRE | Nanoscience
Sabyasachi Dasgupta, Prof. Gerhard Gompper, and Dr. Thorsten Auth (left to right) investigated the influence of edges, side lengths, and curvatures on the implantation of nanoparticles in cells.
tures and side lengths. They analysed the conditions under which membranes wrap around nanoparticles either completely or only partially. They also looked at the conditions under which this does not occur at all or particles get stuck in the boundary layer. To do so, they developed a mathematical relation that enabled them to make predictions. “The intensity of the relationship between the cell and the nanoparticle depends on the ratio of the particle’s length to its width as well as on the curvature of the tiny particle’s edges,” says Gompper. Knowledge for nanomedicine The knowledge thus gained on the perfect “passer-by” is a further step towards future nanopharmaceuticals. Some background information: many processes in the human body take place on a tiny level – the nanolevel. For example, a cell takes up nutrients and discards toxins again by cutting off tiny bubbles that enter or leave the cell. To illustrate how inconceivably small nanoparticles are, we can compare them with the diameter of a human hair; nanoparticles are around 10,000 times smaller. Nanoscientists are eager to make use of the insights obtained into the processes in the human organism. Their vision is to use minute implanted particles of active substances to fight diseases directly at their place of origin. Special
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coatings on the nanopharmaceuticals ensure that the tiny particles will only be taken up by a certain type of cell. Jülich’s latest investigations will help to design particles from suitable materials in future so that they will either only adhere to the membrane in the form of sensor
molecules – for example in the field of drug-loaded nanoparticles in oncology research – or else be completely absorbed in the form of active pharmaceutical substances. :: Ilse Trautwein
Nanomedicine to combat cancer Many oncology patients suffer from severe side effects associated with modern forms of treatment such as chemotherapy. They hope for new treatments with few side effects as soon as possible. Nanotechnology is one option: active substances will be “fired” – like nanomissiles – directly into tumour cells, where they will selectively destroy diseased tissue. For example, a promising treatment method currently in the test phase makes use of the magnetic properties of nanoparticles made from iron oxide. These are injected directly into the tumour. A magnetic field is then generated around the tissue. The nanoparticles absorb the energy from the magnetic field and convert it to heat, which in turn de-
stroys the tumour tissue. European authorization has already been received for this treatment. However, it will take several years for the innovative cancer treatment to overcome all of the subsequent hurdles of clinical trials and win widespread acceptance in hospitals.
In chemotherapy, additional treatment methods are often required to relieve side effects.
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Nanomedicine: Somewhere Between Hype and Hope
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reat hopes are pinned on nanotechnology. It is believed that in future, it will enable diseases such as cancer or diabetes to be identified in good time and treated successfully. Prospects range from nanomaterials that promote the growth of new skin or bone in the body to nanopharmaceuticals that restore optic nerves in blind people. Prof. Dr. rer. nat. Wolfgang M. Heckl, professor at Technische Universität München and Director General of Deutsches Museum, shares his thoughts on the subject. For years, he has been an advisor to the German federal government and the European Commission in the field of nanotechnology.
Prof. Heckl, a great deal is expected of nanomedicine. How realistic are these expectations?
toothpaste containing minute particles that fill tiny cavities in your teeth. However, it all depends on how you define “nano” – in this sense, the figures vary somewhat. In scientific terms, the definition of nanotechnology only applies to applications with nanoparticles smaller than 100 nanometres, whose effects are based on their nanoscale nature. How big is the nanomedicine market? According to a study on nanomedicine released by Bionest Partners last year, there are 230 products on the market or in clinical trials, and this figure is on the rise. Recent analyses suggest that by 2016, the international nanomedicine market will have doubled in size within the space of five years. The estimated market value will then be $ 97–129 million.
In which field of medicine are nanotechnological developments at an advanced stage? Most potential applications are in the field of oncology. Nanoparticles can be used to both diagnose and treat cancer. But – to use a popular metaphor – there is still a long way to go before we can send tiny nano-submarines on missions into the body to perform medical operations. This interview was conducted by Ilse Trautwein.
Many of the ideas circulating in the media are fantasies and still a long way from current research and clinical application. The fact is that in many areas, nanomedicine is unfortunately still in its infancy. What is the reason for this? This is primarily because to this very day, we still do not understand the molecular principles behind many of the processes in the human body. We need this foundation, however, in order to use nanotechnology to improve the diagnosis and treatment of diseases. That is why research projects focusing on the interaction between cells and nanoparticles – such as those by Prof. Gompper’s team at Jülich – are so important.
“There is still A long way to go before we can send tiny nano- submarines on missions into the body to perform medical operations.”
Are there any nanoproducts already on the market today? Of course. Just think of plasters with silver particles that kill bacteria, or nano
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Prof. Wolfgang M. Heckl, nanotechnology advisor to the German federal government and the European Commission
Research in Jülich 2 | 2014
RESEARCH AT THE CENTRE | Climate Research
Something in the Air over Spa Town? Bad Homburg is concerned about its clean air. Why? Because of nitrogen oxide and particulate matter. At the request of the town’s authorities, Jülich climate researchers are searching for the causes of the pollution.
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ad Homburg’s traditional advertising slogan – “air of champagne” – emphasizes the exhilarating effects of its air. But town officials are worried: measurements by the German National Meteorological Service (DWD) show that nitrogen oxide values exceed the limit – 18 µg/m3 of air – and that the town’s certification as a top-class spa town is at risk. Bad Homburg has therefore commissioned scientists from Jülich’s Institute of Energy and Climate Research – Troposphere (IEK-8) to investigate the level of pollutants in the air. The measurement campaign, which concentrates on nitrogen oxide and particulate matter, was launched in February and will last until July. Initial interim results indicate that the principle cause of Bad Homburg’s problems is road traffic. The scientists aim to present their final report by the end of the year. “Our task is to collect data, inform the town of the cause of the air pollution, and provide it with the necessary information to take countermeasures,” says Prof. Andreas Wahner, director at IEK-8. Since February, his colleagues Dr.
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Dieter Klemp and Dr. Christian Ehlers have been hard at work: they are in charge of Jülich’s measurement laboratory, which has been set up at the edge of the spa gardens. This is where they record meteorological data such as temperature, wind direction and speed, and the radiation intensity of the sun. They also measure the concentrations of hydrocarbons, nitrogen oxides, carbon monoxide, formaldehyde, and ozone, as well as particulate matter pollution and the proportion of diesel soot it contains. With a mobile laboratory called “Mobilab”, the atmospheric researchers conduct measurements outside of Bad Homburg to find out which pollutants are being brought into the town. To this end, Klemp and Ehlers use Mobilab to determine the level of nitrogen oxides and particulate matter in the air at various locations in the surrounding area. In April, the town presented the measurement campaign at a press conference. At the time, Andreas Wahner provided an initial assessment: “Measurements taken so far indicate that the principal cause of air pollution in Bad
Prof. Andreas Wahner (left) explained the measurements conducted with “Mobilab”, Jülich’s mobile measurement laboratory, to Lord Mayor of Bad Homburg Michael Korwisi.
Homburg is road traffic.” The measurements showed particularly high levels of nitrogen oxides and particulate matter during rush hour. The scientist estimated that the percentage of soot particles in the particulate matter – 20–30 % – was caused by domestic heating, i.e. radiators and open fireplaces, and by road traffic. The measurement results will be incorporated into simulations of pollutant levels. These will show the expected air quality in seven and in twenty years if the current situation remains the same. However, they will also help to illustrate the potential impacts of individual projects such as traffic management measures or the conversion of heating systems in Bad Homburg. :: Erhard Zeiss
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hough they could have jumped for joy, at first they weren’t allowed to tell anyone when, at the end of March, Stephan Binder and Georg Schendzielorz from the Institute of Bio- and Geosciences (IBG-1) found out that they were to receive € 2.6 million for their business spin-off. The two Jülich biotechnologists had been selected from 106 applications as winners of the GO-Bio competition for business spin-offs instituted by the Federal Ministry of Education and Research (BMBF). The scientists, who recently completed their PhDs, were awarded the prize money as initial funding to bring their special sensor system for a fast and targeted search for highly productive microorganisms to the market and found a company. They had to keep their victory a secret for a few days, as the winners had not yet been officially announced. “It was almost surreal,” recalls Schendzielorz.
production methods in demand It became obvious that their method – which makes highly productive cells glow, thus making them stand out from millions of others – was on the right track in summer 2013, when they received the Innovation Award of the German BioRegions. Funding from the Helmholtz Enterprise initiative followed in December. With these funds, the postdocs laid careful preparations for their spin-off company, developed a viable business model, met with potential customers, created a business plan, and submitted their application to GO-Bio – and met with success. “It’s been a dream come true for us,” they both say. Binder and Schendzielorz jointly developed the technology, which is known as High-Throughput Screening & Recombineering (HTSR), during their PhDs. The basic idea is as follows: In industrial or “white” biotechnology, microorganisms produce active ingredients for drugs, foodstuffs, and chemical substances. The more of the desired substance they produce, the more effective the entire industrial process. There is a growing demand for such organisms due to the increasing number of bio-based produc-
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In a matter of seconds, the FACS (fluorescence-activated cell sorter) sorts the individual bacterial cells into culture tubes or microtitre plates. On the “flower plates” (large image), the bacteria can be cultivated and analysed.
Glow of Satis faction as Dream Comes True Initial funding of € 2.6 million: biotechnologists Stephan Binder and Georg Schendzielorz have won the GO-Bio competition for business spin-offs. Their sensor system for a targeted search for highly productive microorganisms could help to produce promising anticancer substances that are as yet almost impossible to synthesize chemically.
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RESEARCH AT THE CENTRE | Biotechnology
“With conventional methods, you can examine 1,000–2,000 cultures per month; we can analyse 50,000 individual cells per second.”
Two scientists, one business idea: Stephan Binder and Georg Schendzielorz (right) from the Institute of Bioand Geosciences are among the winners of the GO-Bio competition for business spin-offs.
tion methods. But how do you distinguish the few extremely productive cells from the millions of others? Conventional methods require weeks or even months to isolate and cultivate the bacteria. “With HTSR, we can do it in a few days,” says Binder. To track down the most hardworking cells, the scientists implant a circular DNA molecule into the cell. Ultimately, this genetic extra causes all those cells producing the desired substance to glow – the principle being that the more productive the cell, the more fluorescent it is. A device usually used to analyse blood continuously flushes individual microorganisms – at a rate of 50,000 bacteria per second – past a laser beam, which individually sorts the brightest cells in a microtitre plate. There, each selected bacterium multiplies and is then examined further. The scientists have already demonstrated the method’s efficacy for the development of bacterial strains for amino acid production. “We want to consolidate our technology and transfer it to other production organisms, for example for the manufacture of industrial products such as polymer precursors,” ex-
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plains Binder. The resulting biopolymers could replace oil-based products such as plastic bags. Myxobacteria to fight cancer Another of the Jülich colleagues’ major goals is to extend the technology to pharmaceutical products. They have set their sights on anticancer substances, known as cytostatics, which are produced by microorganisms. A strain of soil bacteria looks very promising in this regard. These myxobacteria produce extremely small quantities of various substances that can kill living cells or stop them from growing. One example is epothilone B, an active ingredient that has already been in use for several years to treat breast cancer. “Although there are other promising developments with myxobacteria, they cannot be continued, as the active ingredient could not be produced in sufficient quantities for clinical studies,” says Binder. He and Schendzielorz are putting their faith in HTSR to make the most productive myxobacteria glow and thus pave the way for the development of more effective bacterial strains.
The two biotechnologists have big ambitions. In addition to their innovative ideas and passion for research, they are motivated to explore new avenues by the positive response they have received from industry. “We have spoken with companies like Bayer, Evonik, and BASF – all of whom expressed strong interest,” says Schendzielorz. In autumn, they and four employees will be moving to new facilities at Forschungszentrum Jülich. From there, the research group will make the microorganisms glow for as long as it takes to ready their prototype for the market. Katja Lüers
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Obtaining valuable specialized fertilizers from manure instead of disposing of it laboriously – such is the goal of an international research group.
Gold Mine in the Cowshed A team of scientists and engineers from eleven European institutions are on a hunt for treasure. Their destination: the slurry pit. The goal: customized, sustainable, and environmentally friendly fertilizer. Jülich plant researchers are part of the search team.
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gricultural historians estimate that both human and animal waste has been used to improve harvests for over 8,000 years. However, there is no comparison between the practices of the small farmers of the past and the mass dimensions of modern factory farms. Today, over one billion tonnes of manure are produced each year in the European Union alone. And not all of it can be spread on the fields as fertilizer. The desire to make use of this valuable raw material while preventing environmental pollution is the force driving the scientists in the “Manure EcoMine” project. Their goal is to use
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manure, a natural product, in a more environmentally friendly and specific way. The European Union has allocated € 3.8 million to the project for the next three years. Using up leftovers At the moment, a significant proportion of the manure produced is sent to biogas facilities and provides energy in the form of biogas. However, a product known as digestate is left over, which either can also be used as fertilizer or else must be disposed of at considerable expense. “Whatever feed goes in at one end comes out the other end,” says Dr.
Dr. Nicolai David Jablonowski is testing the effectiveness of the new fertilizer in promoting plant growth.
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RESEARCH AT THE CENTRE | Bioeconomy
Nicolai David Jablonowski from Jülich’s Institute of Bio- and Geosciences – Plant Sciences (IBG-2). Depending on the type of feedstuff, therefore, the chemical composition of both the manure and the digestate varies considerably. Digestates with a high phosphate and nitrate content, for example, result from a mixture of fermented cereal grains and poultry manure. Smaller proportions of these two plant nutrients are produced by a biogas facility supplied with silage maize and cattle manure. For this reason, it is not yet possible to create a specific fertilizer for particular crop types either with manure or with digestates. Either too many or too few important plant nutrients such as nitrogen, phosphate, or potassium end up on the fields. European farmers therefore spend around € 15.5 billion on synthetic fertilizers each year in order to maintain stable harvests. The researchers in the ManureEcoMine project are confident that replacing a large proportion of the synthetic fertilizers with nutrients from manure would be both cost-effective and environmentally friendly. This involves first separating the valuable substances from the manure and then, in a second stage, recombining them depending on the intended purpose. Composing fertilizer This is to be achieved with the aid of biological, physical, and chemical processes. The scientists use the well-known methods of fermentation, centrifugation, and precipitation as a basis. “We believe it’s important to establish a sustainable process chain,” stresses Nicolai David Jablonowski. “Ideally, the energy the farmer obtains from his biogas facility would be used to separate the nutrients from the manure, and the result would be a bag of specialized fertilizer.” Pilot facilities in the Netherlands and Spain are currently testing potential methods of separating the desired constituents from the manure. At a later stage, Peltracom, a Belgian company specializing in potting soils, will take the individual materials and compose different substrate blends – which will be mixed with different quantities of nutrients from the manure as required. These will then be tested at Jülich on crops and
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In the EU,
1.27 billion
tonnes of manure are produced every year
ornamental plants, such as maize, tomatoes, or petunias. At the same time, the new fertilizer must compete with untreated manure and synthetic fertilizers. The effect of the different fertilizers on plant growth above and below ground will be investigated in detail in the inter-
nationally unique rhizotron facility at Jülich. With cameras, plant growth will be recorded continually and evaluated objectively. Using natural resources The project is coordinated by Ghent University in Belgium. Prof. Dr. Siegfried Vlaeminck from the university’s Laboratory of Microbial Ecology and Technology (LanMET) says: “Throughout the entire project, we will focus particular attention on economic efficiency as well as on environmental compatibility and life cycle assessment.” It goes without saying that the end product will also be free of any harmful substances such as heavy metals or pharmaceutical or hormone residues. :: Brigitte Stahl-Busse
An abundance of manure
Today in the European Union, 1.27 billion tonnes of manure are produced each year. To protect the environment, the EU Nitrates Directive restricts the nitrogen input to 170 kg per hectare and year. Up to the end of 2013, German farmers, under certain conditions, could apply up to 230 kg of nitrogen per hectare from fertilizers of animal origin on intensively farmed grassland. This has now been brought to an end. The EU is urging the national legislator to revise the German regulation on fertilizers (Düngeverordnung). Rising nitrate levels in the groundwater in regions with intensive farming prove that urgent action is required. In a recent statement, the German Federal Environment Agency announced that groundwater in Germany’s rural areas contains too much nitrate. Consumers are currently footing the bill, as uncontaminated water has to be added at the waterworks in the affected regions.
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Art from a Supercomputer The photograms currently on display at the Museum of Contemporary Art (S.M.A.K.) in Ghent, Belgium, are the result of a most unusual collaboration. Artist Thomas Ruff teamed up with researchers from the Jülich Supercomputing Centre (JSC) to produce them. 22
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LAST BUT NOT LEAST
Publication Details
Exhibition The photograms by Thomas Ruff that were computed at Jülich are being exhibited at S.M.A.K. until 24 August. In September they will go on display in Düsseldorf.
The artist and his work: Thomas Ruff’s photograms were created entirely on a computer.
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he idea originated nearly a year ago. The internationally acclaimed artist Thomas Ruff was working on a new series – photograms. Strictly speaking, these are blackand-white photographic images created without a camera in a darkroom. To do so, objects are arranged on light-sensitive paper and exposed to light. The shadows produce fascinating patterns. Ruff introduced photograms to the digital age: his images were created in a kind of virtual darkroom on a computer. “Unlike in the analogue world, this makes it possible to produce colour photograms. Objects and light sources can also be modified much more quickly and easily, and the images aren’t restricted to the size of the photographic paper,” explains the 56-year-old. His photograms can reach sizes of 2.20 m x 1.64 m – which corresponds to at least nine gigabytes of data per image. This pushes ordinary computers to their limits. “At some point I simply want-
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ed to compute one of my images on a supercomputer,” says Ruff. The goal was to produce photograms with even better resolution and the highest possible quality. He therefore got in touch with JSC. “From our point of view, the high demands for data storage, data rates, and local processing power provided us with an ideal opportunity to determine important characteristics for the design of the computer to succeed the JUROPA system,” says Prof. Thomas Lippert, head of JSC. “It was also a good occasion to get people other than our usual clientele interested in high-performance computing.” For some three months, Thomas Ruff and JSC worked together in close cooperation. The artist is thrilled with the results of the 20 photograms, saying: “The improvement in the contrasts and intricate structures alone is extraordinary.” The fact that the higher resolution led to data sizes of at least 18 terabytes per image was no problem for JUROPA: the supercomputer required a maximum of 15 hours to compute one image. It would have taken Ruff’s computer over a year.
Research in Jülich Magazine of Forschungszentrum Jülich, ISSN 1433-7371 Published by: Forschungszentrum Jülich GmbH | 52425 Jülich | Germany Conception and editorial work: Annette Stettien, Dr. Barbara Schunk, Dr. Anne Rother (responsible according to German press law) Authors: Dr. Frank Frick, Christian Hohlfeld, Katja Lüers, Christoph Mann, Tobias Schlößer, Dr. Barbara Schunk, Brigitte Stahl-Busse, Ilse Trautwein, Angela Wenzik, Erhard Zeiss Translation: Language Services | Forschungs zentrum Jülich Graphics and layout: SeitenPlan GmbH, Corporate Publishing, Dortmund | Germany Images: Deutsches Museum (16); Forschungs zentrum Jülich (2, 3 centre and right, 4 top left, 5 top, 12 left and right, 14, 15 top, 18 left and right, 19 right, 20 bottom, 23 bottom); Forschungszentrum Jülich/Sascha Kreklau (cover page, 3 left, 6, 7, 9–11); Justin Marshall (4 top right); Nature Methods/Sharon Grayer Wolf, Lothar Houben & Michael Elbaum (4 bottom); SeitenPlan GmbH (8, 13); Town of Bad Homburg (17 bottom); VG Bild Kunst Bonn, 2014 (22, 23 top left and top right); Jo Chambers (17 top), fotoscool (24), hjschneider (21), Image Point Fr (15 bottom), Lumir Jurka Lumis (5 bottom), Symbiot (20 top), all from Shutterstock.com Contact: Corporate Communications | Tel: +49 2461 61-4661 | Fax: +49 2461 61-4666 | Email: info@fz-juelich.de
Christian Hohlfeld
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