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Highly-Efficient Photoelectrochemical CO2 Reduction
Direct CO2 conversion has continuously attracted a great deal of attention as a technology to produce fuels and chemical building blocks from renewable energy resources. Specifically, substances such as carbon feedstocks and fuels can be produced by utilizing sunlight, water, and CO2 as semiconductors and a water interface through photoelectrochemical CO2 reduction. A KAIST research team demonstrated a novel photoelectrode structure for highly-selective and efficient photoelectrochemical CO2 reduction reactions. The research team led by Professor Jihun Oh of the Graduate School of EEWS (Energy, Environment, Water and Sustainability) presented a Si photoelectrode with a nanoporous Au thin film that is capable of reducing CO2 to CO with 90 percent selectivity in aqueous solution. The research team’s technology will provide a basic framework for designing the semiconductor photoelectrode structure necessary for photoelectrochemical conversion. In order to achieve steady conversion of CO2, it is necessary to use a high-performance catalyst to lower overpotential. Among the metal catalysts, Au is known to be an electrocatalyst that converts CO2 to CO. Conventionally, bare Au, as a catalyst, produces a lot of hydrogen gas due to its low CO selectivity. In addition, the high cost of Au remains a challenge in using the catalyst. Professor Oh’s research team addressed the issue by creating a nanoporous Au thin film formed by the electrochemical reduction of an anodized Au thin film. As a result, the team could demonstrate an efficient, selective photoelectrochemical reduction reaction of CO2 to CO using electrochemically-treated Au thin films on a Si photoelectrode. The electrochemical reduction on anodized Au thin films forms a nanoporous thin layer exhibiting many grain boundaries of nanoparticles on the Au surface. This dramatically improves the selectivity of the reduction reaction with a maximum CO faradaic efficiency of over 90% at low overpotential and durability. The research team also used an Au thin film of about 200 nanometers, 50,000 times thinner than previously reported nanostructured Au catalysts, resulting in a cost-effective catalyst. When depositing the catalyst on the semiconductor surface in the type of nanoparticles, the substrate of the thin film will be affected in the course of electrochemical reduction. Thus, the research team designed a new Si photoelectrode with mesh-type co-catalysts that are independently wired at the front and back of the photoelectrode without influencing the photoelectrode, and made it possible for electrochemical reduction. Due to the superior CO2 reduction reaction activity of the nanoporous Au mesh and high photovoltage from Si, the Si photoelectrode with the nanoporous Au thin film mesh shows conversion of CO2 to CO with 91% Faradaic efficiency at positive potential than CO equilibrium potential. Professor Oh explained, “This technology will serve as a platform for diverse semiconductors and catalysts. Researchers can further improve the solar-to-CO2 conversion efficiency using this technology. Dr. Jun Tae Song, the first author continued, “This new approach made it possible to develop a simple but very important type of electrode structure. It is the first time to achieve CO2 conversion at the potential lower than equilibrium potential. We believe that our research will contribute to efficient CO2 conversion.” This research was published in the inside front cover of Advanced Energy Materials on February 8, 2017. The research was funded and supported by the Korea Carbon Capture & Sequestration R&D Center. Professor Sung-Yoon Chung of the EEWS also participated in this research. (Figure: Schematic diagram of a Si photoelectrode that patterns with mesh-type nanoporous Au)
2017.03.08
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Semiconductor Photonic Nanocavities on Paper Substrates
Professor Yong-Hoon Cho of the Department of Physics and his team at KAIST have developed a semiconductor photonic nanocavity laser that can operate on a paper substrate. The researchers hope that this novel method, which involves transferring nano-sized photonic crystal particles onto a paper substrate with high absorptiveness, will enable the diagnoses of various diseases by using high-tech semiconductor sensors at low cost. The results of this research were published in the November 17th, 2016, issue of Advanced Materials. Photonic crystals, which utilize light as a medium to provide high bandwidths, can transfer large amounts of information. Compared with their electronic counterparts, photonic crystals also consume less energy to operate. Normally, semiconductor photonic particles require substrates, which play only a passive role in the assembly and endurance of individual, functional photonic components. These substrates, however, are bulky and environmentally hazardous as they are made up of non-biodegradable materials. The research team overcame these two shortcomings by replacing a semiconductor substrate with standard paper. The substrate’s mass was reduced considerably, and because paper is made from trees, it degrades. Paper can be easily and cheaply acquired from our surroundings, which drastically reduces the unit cost of semiconductors. In addition, paper possesses superior mechanical characteristics. It is flexible and can be repeatedly folded and unfolded without being torn. These are traits that have long been sought by researchers for existing flexible substrates. The research team used a micro-sized stamp to detach photonic crystal nanobeam cavities selectively from their original substrate and transfer them onto a new paper substrate. Using this technique, the team removed nanophotonic crystals that had been patterned (using a process of selectively etching circuits onto a substrate) onto a semiconductor substrate with a high degree of integration, and realigned them as desired on a paper substrate. The nanophotonic crystals that the team combined with paper in this research were 0.5 micrometers in width, 6 micrometers in length, and 0.3 micrometers in height—about one-hundredth of the width of a single hair (0.1 millimeter). The team also transferred their photonic crystals onto paper with a fluid channel, which proved that it could be used as a refractive index sensor. As can be seen in current commercial pregnancy diagnosis kits, paper has high absorptiveness. Since photonic crystal particles have high sensitivity, they are highly suitable for applications such as sensors. Professor Cho stated that “by using paper substrates, this technology can greatly contribute to the rising field of producing environmentally-friendly photonic particles” and “by combining inexpensive paper and high-performance photonic crystal sensors, we can obtain low prices as well as designing appropriate technologies with high performance.” Dr. Sejeong Kim of the Department of Physics participated in this study as the first author, and Professor Kwanwoo Shin of Sogang University and Professor Yong-Hee Lee of KAIST also took part in this research. The research was supported by the National Research Foundation’s Mid-Career Researcher Program, and the Climate Change Research Hub of KAIST. Figure 1. Illustration of photonic crystal lasers on paper substrates Figure 2. Photonic crystal resonator laser and refractive index sensor operating on paper substrates
2017.03.01
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Quantum Dot Film Can Withstand High Temperatures and Humidity
The joint KAIST research team of Professor Byeong-Soo Bae of the Department of Materials Science and Engineering and Professor Doh Chang Lee of the Department of Chemical and Biomolecular Engineering was able to fabricate a siloxane-encapsulated quantum dot film, which exhibits stable emission intensity over one month even at high temperatures and humidity. The results of this study were published in the Journal of the American Chemical Society (JACS) on November 29, 2016. The research article is entitled “Quantum Dot/Siloxane Composite Film Exceptionally Stable against Oxidation under Heat and Moisture.” (DOI: 10.1021/jacs.6b10681) Quantum dots (QDs), light-emitting diodes (LEDs) for next-generation displays, are tiny particles or nanocrystals of semiconducting materials. Their emission wavelength can easily be adjusted by changing their sizes, which are just a few nanometers. A wide spectrum of their colors can also achieve ultra-high definition displays. Due to these characteristics, QDs are coated on a film as a polymer resin in dispersed form, or they are spread on an LED light source. They are thus considered to be crucial for next generation displays. Despite their exceptional optical properties, however, QDs are easily oxidized in a high temperature and high humidity environment, and, as a result, this greatly deteriorates their luminescence quality (quantum efficiency). Therefore, they are encapsulated in an extra thin layer to block oxygen and moisture. QD displays in the current market have a film inserted to separate them from LEDs, which create heat. The high unit cost of this protective layer, however, increases the overall cost of displays, lowering their price competitiveness in the market. For a solution, the research team applied the sol-gel condensation reaction of silane precursors with QDs. This technology uses the reactions of chemical substances to synthesize ceramics or glass at a low temperature. The team applied QDs in a heat resistant siloxane polymer by employing this technology. The siloxane resin acted as a cup holding the QDs and also blocked heat and moisture. Thus, their performance can be maintained without an extra protective film. QDs are evenly dispersed into the resin from a chemical process to fabricate a QD embedded film and retained the high quality luminescence not only at a high temperature of 85°C and in a high humidity of 85%, but also in a high acid and high base environment. Remarkably though, the luminescence actually increased in the high humidity environment. If this technology is used, the overall price of displays will decrease by producing a stable QD film without an extra protective barrier. In the future, the QD film can be directly applied to a blue LED light source. As a result, it will be possible to develop a QD display that can reduce the amount of QDs needed and improve its performance. Professor Bae said, “We have proposed a way to make quantum dots overcome their limitations and have wide applications as they are being developed for next-generation displays. Our technology will make significant contributions to the display industry in the country.” He also added, “In the future, we plan to cooperate with companies both in and out of the country to improve the performance of quantum dots and concentrate on their commercialization.” The research team is currently applying for related patents both in and out of the country. The team is also plan ning to transfer the patents to Sol Ip Technology Inc., a company founded at KAIST, to start the commercialization. Picture 1: Siloxane-encapsulated quantum dot (QD) films showing performance stability in boiling water Picture 2 and 3: So-gel condensation reaction in silane precursors between Methacryloxypropyltrimethoxysilane (MPTS) and diphenylsilanediol (DPSD). The inset shows photographs of a QD-oligosiloxane resin under room light (left) and a UV lamp (λ = 365 nm) (right). Free radical addition reactions among carbon double bonds of methacryl functional groups and oleic acids. The inset shows photographs of a QD-silox film under room light (left) and a UV lamp (λ = 365 nm) (right).
2017.02.24
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Controlling Turtle Motion with Human Thought
KAIST researchers have developed a technology that can remotely control an animal’s movement with human thought. In the 2009 blockbuster “Avatar,” a human remotely controls the body of an alien. It does so by injecting human intelligence into a remotely located, biological body. Although still in the realm of science fiction, researchers are nevertheless developing so-called ‘brain-computer interfaces’ (BCIs) following recent advances in electronics and computing. These technologies can ‘read’ and use human thought to control machines, for example, humanoid robots. New research has demonstrated the possibility of combining a BCI with a device that transmits information from a computer to a brain, or known as a ‘computer-to-brain interface’ (CBI). The combination of these devices could be used to establish a functional link between the brains of different species. Now, researchers from the Korea Advanced Institute of Science and Technology (KAIST) have developed a human-turtle interaction system in which a signal originating from a human brain can affect where a turtle moves. Unlike previous research that has tried to control animal movement by applying invasive methods, most notably in insects, Professors Phill-Seung Lee of the Mechanical Engineering Department and Sungho Jo of the Computing School propose a conceptual system that can guide an animal’s moving path by controlling its instinctive escape behavior. They chose a turtle because of its cognitive abilities as well as its ability to distinguish different wavelengths of light. Specifically, turtles can recognize a white light source as an open space and so move toward it. They also show specific avoidance behavior to things that might obstruct their view. Turtles also move toward and away from obstacles in their environment in a predictable manner. It was this instinctive, predictable behavior that the researchers induced using the BCI. The entire human-turtle setup is as follows: A head-mounted display (HMD) is combined with a BCI to immerse the human user in the turtle’s environment. The human operator wears the BCI-HMD system, while the turtle has a 'cyborg system'—consisting of a camera, Wi-Fi transceiver, computer control module, and battery—all mounted on the turtle’s upper shell. Also included on the turtle’s shell is a black semi-cylinder with a slit, which forms the ‘stimulation device.’ This can be turned ±36 degrees via the BCI. The entire process works like this: the human operator receives images from the camera mounted on the turtle. These real-time video images allow the human operator to decide where the turtle should move. The human provides thought commands that are recognized by the wearable BCI system as electroencephalography (EEG) signals. The BCI can distinguish between three mental states: left, right, and idle. The left and right commands activate the turtle’s stimulation device via Wi-Fi, turning it so that it obstructs the turtle’s view. This invokes its natural instinct to move toward light and change its direction. Finally, the human acquires updated visual feedback from the camera mounted on the shell and in this way continues to remotely navigate the turtle’s trajectory. The research demonstrates that the animal guiding scheme via BCI can be used in a variety of environments with turtles moving indoors and outdoors on many different surfaces, like gravel and grass, and tackling a range of obstacles, such as shallow water and trees. This technology could be developed to integrate positioning systems and improved augmented and virtual reality techniques, enabling various applications, including devices for military reconnaissance and surveillance. *** Reference: “Remote Navigation of Turtle by Controlling Instinct Behavior via Human Brain-computer Interface,” Journal of Bionic Engineering, July 2016 (DOI: 10.1016/S1672-6529(16)60322-0) Depiction of Cyborg System A human controller influences the turtle’s escape behavior by sending left and right signals via Wi-Fi to a control system on the back of the turtle.
2017.02.21
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An Improved Carbon Nanotube Semiconductor
Professor Yang-Kyu Choi and his research team of the School of Electrical Engineering at KAIST collaborated with Professor Sung-Jin Choi of Kookmin University to develop a large-scale carbon nanotube semiconductor by using a 3-D fin-gate structure with carbon nanotubes on its top. Dong Il Lee, a postdoctoral researcher at KAIST’s Electrical Engineering School, participated in this study as the first author. It was published in ACS Nano on November 10, 2016, and was entitled “Three-Dimensional Fin-Structured Semiconducting Carbon Nanotube Network Transistor.” A semiconductor made with carbon nanotubes operates faster than a silicon semiconductor and requires less energy, yielding higher performance. Most electronic equipment and devices, however, use silicon semiconductors because it is difficult to fabricate highly purified and densely packed semiconductors with carbon nanotubes (CNTs). To date, the performance of CNTs was limited due to their low density. Their purity was also low, so it was impossible to make products that had a constant yield on a large-surface wafer or substrate. These characteristics made the mass production of semiconducting CNTs difficult. To solve these difficulties, the research team used a 3-D fin-gate to vapor-deposit carbon nanotubes on its top. They developed a semiconductor that had a high current density with a width less than 50 nm. The three-dimensional fin structure was able to vapor-deposit 600 carbon nanotubes per micrometer. This structure could have 20 times more nanotubes than the two dimensional structure, which could only vapor-deposit thirty in the same 1 micrometer width. In addition, the research team used semi-conductive carbon nanotubes having a purity rating higher than 99.9% from a previous study to obtain a high yield semiconductor. The semiconductor from the research group has a high current density even with a width less than 50 μm. The new semiconductor is expected to be five times faster than a silicon-based semiconductor and will require five times less electricity during operation. Furthermore, the new semiconductor can be made by or will be compatible with the equipment for producing silicon-based semiconductors, so there will be no additional costs. Researcher Lee said, “As a next generation semiconductor, the carbon nanotube semiconductor will have better performance, and its effectiveness will be higher.” He also added, “Hopefully, the new semiconductor will replace the silicon-based semiconductors in ten years.” This study received support from the Center for Integrated Smart Sensors funded by the Ministry of Science, ICT & Future Planning of Korea as the Global Frontier Project, and from the CMOS (Complementary Metal-Oxide-Semiconductor) THz Technology Convergence Center of the Pioneer Research Center Program sponsored by the National Research Foundation of Korea. Picture 1: 3D Diagram of the Carbon Nanotube Electronic Device and Its Scanning Electron Microscope (SEM) Image Picture 2: 3D Transistor Device on an 8-inch Base and the SEM Image of Its Cross Section
2017.02.16
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A New Approach to 3D Holographic Displays Greatly Improves the Image Quality
With the addition of holographic diffusers or frosted glasses to wavefront modulators, KAIST researchers offer a simple and practical solution to significantly enhance the performance of 3D dynamic holographic displays by 2,600 times. The potential applications of three-dimensional (3D) digital holograms are enormous. In addition to arts and entertainment, various fields including biomedical imaging, scientific visualization, engineering design, and displays could benefit from this technology. For example, creating full-sized organs for 3D analysis by doctors could be helpful, but it remained a challenge owing to the limitation of hologram-generation techniques. A research team led by Professor YongKeun Park of the Physics Department at KAIST has come up with a solution and developed a 3D holographic display that performs more than 2,600 times better than existing 3D holographic displays. This study is expected to improve the limited size and viewing angle of 3D images, which were a major problem of the current holographic displays. The study was published online in Nature Photonics on January 23, 2017. 3D holograms, which often appear in science fiction films, are a familiar technology to the public, but holograms in movies are created with computer graphic effects. Methods for creating true 3D holograms are still being studied in the laboratory. For example, due to the difficulty of generating real 3D images, recent virtual reality (VR) and augmented reality (AR) devices project two different two-dimensional (2D) images onto a viewer to induce optical illusions. To create a 3D hologram that can be viewed without special equipment such as 3D glasses, the wavefront of light must be controlled using wavefront modulators such as spatial light modulators (SLMs) and deformable mirrors (DMs). A wavefront modulator is an optical manipulation device that can control the direction of light propagation. However, the biggest limitation to using these modulators as 3D displays is the number of pixels. The large number of pixels that are packed into high-resolution displays developed in recent years are suitable for a 2D image, and the amount of information contained in those pixels cannot produce a 3D image. For this reason, a 3D image that can be made with existing wavefront modulator technology is 1 cm in size with a narrow viewing angle of 3 degrees, which is far from practicable. As an alternative, KAIST researchers used a DM and added two successive holographic diffusers to scatter light. By scattering light in many directions, this allows for a wider viewing angle and larger image, but results in volume speckle fields, which are caused by the interference of multiple scattered light. Random volume speckle fields cannot be used to display 3D images. To fix the problem, the researchers employed a wavefront-shaping technique to control the fields. As a result, they succeeded in producing an enhanced 3D holographic image with a viewing angle of 35 degrees in a volume of 2 cm in length, width, and height. This yielded a performance that was about 2,600 times stronger than the original image definition generated when they used a DM without a diffuser. Professor Park said, “Scattering light has previously been believed to interfere with the recognition of objects, but we have demonstrated that current 3D displays can be improved significantly with an increased viewing angle and image size by properly controlling the scattered light.” Hyeonseung Yu, who is the lead author of this research article and a doctoral candidate in the Department of Physics, KAIST, noted that this technology signals a good start to develop a practical model for dynamic 3D hologram displays that can be enjoyed without the need for special eyeglasses. “This approach can also be applied to AR and VR technology to enhance the image resolution and viewing angles,” added Yu. The research paper is entitled “Ultrahigh-definition Dynamic 3D Holographic Display by Active Control of Volume Speckle Fields.” Figure 1. Concept of Scattering Display The size and viewing angle of 3D images can be simultaneously increased when a scattering medium (diffuser) is introduced. By controlling the wavefront impinging on the scattering medium, the desired 3D hologram is generated. Figure 2. Experimental Setup The optical set-up consists of a deformable mirror and the scattering medium with two successive holographic diffusers. A high-numerical-aperture imaging unit mounted on a three-axis motorized translational system is utilized for wavefront optimization and imaging. Figure 3. 3D Images Projected This picture shows 3D images in a volume of 2 cm × 2 cm × 2 cm with a viewing angle of 35 degrees using one of the wavefront modulators, a digital micromirror device (DMD). Figure 4. Artist’s Rendition of the Proposed Concept A dynamic 3D hologram of a face is displayed.
2017.02.01
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Adsorbent That Can Selectively Remove Water Contaminants
Professor Cafer T. Yavuz and his team at the Graduate School of Energy, Environment, Water, and Sustainability (EEWS) have developed an adsorbent that can selectively capture soluble organic contaminants in water. This water treatment adsorbent is a fluorine-based nanoporous polymer that can selectively remove water-soluble micromolecules. It has the added advantage of being cheap and easily synthesized, while also being renewable. The results of this research have been published online in Nature Communication on November 10, 2016. The research paper is titled “Charge-specific Size-dependent Separation of Water-soluble Organic Molecules by Fluorinated Nanoporous Networks.” (DOI: 10.1038/ncomms13377) Water pollution is accelerating as a result of global industrial development and warming. As new materials are produced and applied in the agricultural and industrial sectors, the types of contaminants expelled as sewage and waste water are also becoming diverse. Chemicals such as dyes and pesticides can be especially harmful because they are made up of small and highly soluble organic particles that cannot be completely removed during the water treatment process, ultimately ending up in our drinking water. The current conventional water treatment systems utilize processes such as activated carbon, ozonolysis, and reverse osmosis membrane. These processes, however, are designed to remove larger organic molecules with lower solubility, thus removal of very small molecules with high solubility is difficult. In addition, these micromolecules tend to be charged, therefore are less easily separated in aqueous form. The research team aimed to remove these small molecules using a new adsorbent technology. In order to remove aqueous organic molecular contaminants, the team needed an adsorbent that can adsorb micro-sized molecules. It also needed to introduce a chemical function that would allow it to selectively adsorb molecules, and lastly, the adsorbent needed to be structurally stable as it would be used underwater. The team subsequently developed an adsorbent of fluorine-based porous organic polymer that met all the conditions listed above. By controlling the size of the pores, this adsorbent is able to selectively adsorb aqueous micromolecules of less than 1-2 nm in size. In addition, in order to separate specific contaminants, there should be a chemical functionality, such as the ability to strongly interact with the target material. Fluorine, the most electronegative atom, interacts strongly with charged soluble organic molecules. The research team incorporated fluorine into an adsorbent, enabling it to separate charged organic molecules up to 8 times faster than neutral molecules. The adsorbent developed by Professor Yavuz’s team has wide industrial applications. It can be used in batch-adsorption tests, as well as in column separation for size- and charge-specific adsorption. Professor Yavuz stated that “the charge-selective properties displayed by fluorine has the potential to be applied in desalination or water treatment processes using membranes." This paper was first-authored by Dr. Jeehye Byun, and the research was funded by KAIST’s High Risk High Return Program and the Ministry of Science, ICT and Future Planning of Korea’s Mid-Career Researcher Program, as well as its Technology Development Program to Solve Climate Change. Figure 1. Diagram conceptualizing the process of charge- and size-specific separation by the fluorine-based porous polymer adsorbent Figure 2. Difference in absorbance before and after using a porous fluorine polymer column to separate organic molecules Figure 3. Adsorption properties of a fluorine polymer according to the charge and size of organic molecules
2017.01.17
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Controlling DNA Orientation Using a Brush
Professor Dong Ki Yoon’s research team in the Graduate School of Nanoscience and Technology has developed a technique for producing periodic DNA zigzag structures using a common make-up brush. The results of the research, first-authored by Ph.D. student Yun Jeong Cha and published in Advanced Materials (online, November 15, 2016), has been highlighted in the hot topics of “Liquid Crystals.” There exist various methods for synthesizing DNA-based nanostructures, but they commonly involved complex design processes and required expensive DNA samples with regulated base sequences. Using DNA materials extracted from salmon, the research team was able to produce a nanostructure with a well-aligned zigzag pattern at one-thousandth of the usual cost. The team used a commercial make-up brush bought at a cosmetics store, and with it, applied the salmon DNA in one direction onto a plate, in the same way paint is brushed onto paper. Using a brush with a width of several centimeters, the team aligned DNA molecules of 2 nanometers in diameter along the direction of the brush strokes. As the thin and dense film of DNA came into contact with air, it lost moisture. An expansive force was created between the dried film and the plate. This force interacted with the elastic force of DNA and caused undulations in the uni-directionally aligned DNA molecules, which resulted in a regular zigzag pattern. The zigzag DNA’s base sequences could not be controlled because it was extracted from biological sources. However, it has the advantage of being cheap and readily available without compromising its structural integrity and provides a very regular and intricate structure. This kind of well-ordered DNA structure can be used as template because it can guide or control versatile guest functional materials that are applied to its surface. For example, it can align liquid crystals used in displays, as well as metallic particles and semi-conductors. It is expected that this capacity can be extended to optoelectric devices in the future. Professor Yoon remarked that “these findings have special implications, as they have demonstrated that various materials in nature aside from DNA, such as proteins, muscle cells, and components of bones can be applied to optoelectric devices.” This research has been carried out with the support of the Korea National Research Foundation’s Nanomaterials Fundamental Technology Development Program and the Pioneer Research Center under the High-tech Convergence Technology Development Program. Source: "Control of Periodic Zigzag Structures of DNA by a Simple Shearing Method" by Yun Jeong Cha and Dong Ki Yoon (Advanced Materials, November 15, 2016, DOI: 10.1002/adma.201604247) Figure 1. Diagram showing the well-ordered zigzag structure of DNA, and the internal molecular orientation Figure 2. (Left) Unaligned DNA (Right) Aligned DNA after being brushed and dried Figure 3. Control of the periodicity of the DNA zigzag patterns using micro-channel plates Figure 4. Diagram representing the control of orientation of liquid crystal materials applied on a zigzag DNA template, and a polarized optical microscope image
2017.01.10
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The Antibody That Normalizes Tumor Vessels
Researchers also discover that their antisepsis antibody reduces glioma, lung and breast cancer progression in mice. A research team at the Center for Vascular Research within the Institute for Basic Science (IBS) discovered that the antisepsis antibody ABTAA (Ang2-Binding and Tie2-Activating Antibody) reduces tumor volume and improves the delivery of anti-cancer drugs. Published in Cancer Cell, this study demonstrates that ABTAA restores the structural and functional integrity of tumor blood vessels in three different tumor models: breast, lungs, and brain. Blood vessels inside and around an established tumor can be described as a chaotic and dysfunctional labyrinth. While the inner walls of healthy blood vessels are surrounded and supported by endothelial cells and other cells called pericytes, in the established tumor, the endothelial junctions are broken apart and pericytes are also detached. Blood flow into and from the tumor is severely retarded and tumor vessels lacking an intact vessel wall become leaky. This microenvironment causes limited drug delivery to the tumor and leads to inadequate oxygen supply (hypoxia) and even metastasis. The research team led by Professor Gou-Young Koh at KAIST’s Graduate School of Medical Science and Engineering found that the antibody ABTAA normalizes the tumor vessels and hence, change the whole tumor microenvironment. “We call it normalization of tumor vessels, because it resembles closely the wall architecture of healthy, normal vessels,” explains PARK Jin-Sung, first author of the study. And continues: “Tumor can adapt to hypoxia and get more aggressive, so we tried to prevent this transition by normalizing tumor vessels. ABTAA changes the whole tumor environment, oxygenation status and level of lactate, so that the immune cells and drugs can reach the core regions of the tumor more easily. In this way, we create a favorable ground for tumor treatment.” In an attempt to generate antibodies targeting the protein Ang2, which is specifically expressed by endothelial cells in stressful conditions like in tumor, the team unexpectedly discovered that ABTAA has a peculiar way of working and a dual function. ABTAA indeed not only blocks Ang2, but also activates Tie2 at the same time. Tie2 is a receptor present on the cell membrane of endothelial cells. ABTAA causes Ang2 to cluster together and to strongly activate Tie2 receptors. “If we activate Tie2, we can efficiently normalize tumor vessels, enhance drug delivery and change the whole microenvironment,” explains KOH Gou Young, Director of the Center for Vascular Research. Several pharmaceutical companies are developing Ang2-blocking antibodies to cure cancer. However, even if these antibodies significantly inhibit tumor progression, they do not stop tumor hypoxia. Moreover, most of the anti-cancer drugs target the tumor at its early stage, when tumors are still hard to diagnose. ABTAA, instead, works with tumors that are already rooted: “When the tumor is established, hypoxia is the main driver of tumor progression. So, if we eliminate hypoxia, we make the tumor milder, by reducing its progression and metastasis,” comments Koh. Figure: Schematic drawing of a blood vessel around tumors before and after treatment with ABTAA. The picture above shows a typical tumor vasculature characterized by damaged walls, red blood cells leakage and detached pericytes. Activating Tie2 on endothelial cells with the antibody ABTAA restores the normal vessel architecture: endothelial and pericytes on the vessel walls are stabilized, the delivery of blood is improved, and the anticancer drugs are more likely to reach the tumor core. The researchers tested ABTAA in mice with three different types of tumors that show high levels of Ang2: glioma (a type of a brain tumor), lung carcinoma, and breast cancer. They also compared the effect of ABTAA with ABA, another antibody that blocks Ang2 but misses the Tie2 activating properties. In all three cases, ABTAA was superior to ABA in inducing tumor vessel normalization, which led to a better delivery of the anti-cancer drugs into the tumor core region. Glioma is one of the so-called intractable diseases, because of its poor prognosis and treatment. Professor Koh’s team found that the glioma volume was reduced 39% by ABTAA and 17% by ABA. ABTAA profoundly reduced vascular leakage and edema formation in glioma through promoting vascular tightening. Moreover, when ABTAA was administered together with the chemotherapeutic drug temozolomide (TMZ), the tumor volume reduces further (76% by ABTAA+TMZ, 51% by ABA+TMZ, and 36% by TMZ). In the Lewis Lung Carcinoma (LLC) tumor model, the team administered ABTAA together with a chemotherapeutic drug called cisplatin (Cpt) and observed a greater suppression of tumor growth (52%) compared with the controls and increased overall survival. Moreover, ABTAA+Cpt led to a marked increase in necrotic area within tumors. Finally, in a spontaneous breast cancer model, ABTAA delayed tumor growth and enhanced the anti-tumor effect of Cpt. Courtesy of the Institute for Basic Sciences (IBS) Figure: The antibody ABTAA alone and in combination with other anti-cancer drugs have a beneficial effect in reducing tumor volume. ABTAA was tested in mice with brain tumor (glioma), lung or breast cancer. The image shows the improvements: reduction in glioma tumor size, reduction in metastatic colonies in lung tumor and decrease in necrotic regions in breast tumor. In the future, the team would like to further understand the underlying relationship between faulty blood vessels and diseases. “We would like to apply this antibody to an organ that is rich in blood vessels, that is the eye, and see if this antibody can be useful to treat eye diseases such as age-related macular degeneration and diabetic retinopathy,” concludes Koh. Professor Gou-Young Koh (left) and Jin-Sung Park (right)
2016.12.16
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Mystery of Biological Plastic Synthesis Machinery Unveiled
Plastics and other polymers are used every day. These polymers are mostly made from fossil resources by refining petrochemicals. On the other hand, many microorganisms naturally synthesize polyesters known as polyhydroxyalkanoates (PHAs) as distinct granules inside cells. PHAs are a family of microbial polyesters that have attracted much attention as biodegradable and biocompatible plastics and elastomers that can substitute petrochemical counterparts. There have been numerous papers and patents on gene cloning and metabolic engineering of PHA biosynthetic machineries, biochemical studies, and production of PHAs; simple Google search with “polyhydroxyalkanoates” yielded returns of 223,000 document pages. PHAs have always been considered amazing examples of biological polymer synthesis. It is astounding to see PHAs of 500 kDa to sometimes as high as 10,000 kDa can be synthesized in vivo by PHA synthase, the key polymerizing enzyme in PHA biosynthesis. They have attracted great interest in determining the crystal structure of PHA synthase over the last 30 years, but unfortunately without success. Thus, the characteristics and molecular mechanisms of PHA synthase were under a dark veil. In two papers published back-to-back in Biotechnology Journal online on November 30, 2016, a Korean research team led by Professor Kyung-Jin Kim at Kyungpook National University and Distinguished Professor Sang Yup Lee at the Korea Advanced Institute of Science and Technology (KAIST) described the crystal structure of PHA synthase from Ralstonia eutropha, the best studied bacterium for PHA production, and reported the structural basis for the detailed molecular mechanisms of PHA biosynthesis. The crystal structure has been deposited to Protein Data Bank in February 2016. After deciphering the crystal structure of the catalytic domain of PHA synthase, in addition to other structural studies on whole enzyme and related proteins, the research team also performed experiments to elucidate the mechanisms of the enzyme reaction, validating detailed structures, enzyme engineering, and also N-terminal domain studies among others. Through several biochemical studies based on crystal structure, the authors show that PHA synthase exists as a dimer and is divided into two distinct domains, the N-terminal domain (RePhaC1ND) and the C-terminal domain (RePhaC1CD). The RePhaC1CD catalyzes the polymerization reaction via a non-processive ping-pong mechanism using a Cys-His-Asp catalytic triad. The two catalytic sites of the RePhaC1CD dimer are positioned 33.4 Å apart, suggesting that the polymerization reaction occurs independently at each site. This study also presents the structure-based mechanisms for substrate specificities of various PHA synthases from different classes. Professor Sang Yup Lee, who has worked on this topic for more than 20 years, said, “The results and information presented in these two papers have long been awaited not only in the PHA community, but also metabolic engineering, bacteriology/microbiology, and in general biological sciences communities. The structural information on PHA synthase together with the recently deciphered reaction mechanisms will be valuable for understanding the detailed mechanisms of biosynthesizing this important energy/redox storage material, and also for the rational engineering of PHA synthases to produce designer bioplastics from various monomers more efficiently.” Indeed, these two papers published in Biotechnology Journal finally reveal the 30-year mystery of machinery of biological polyester synthesis, and will serve as the essential compass in creating designer and more efficient bioplastic machineries. References: Jieun Kim, Yeo-Jin Kim, So Young Choi, Sang Yup Lee and Kyung-Jin Kim. “Crystal structure of Ralstonia eutropha polyhydroxyalkanoate synthase C-terminal domain and reaction mechanisms” Biotechnology Journal DOI: 10.1002/biot.201600648 http://onlinelibrary.wiley.com/doi/10.1002/biot.201600648/abstract Yeo-Jin Kim, So Young Choi, Jieun Kim, Kyeong Sik Jin, Sang Yup Lee and Kyung-Jin Kim. “Structure and function of the N-terminal domain of Ralstonia eutropha polyhydroxyalkanoate synthase, and the proposed structure and mechanisms of the whole enzyme” Biotechnology Journal DOI: 10.1002/biot.201600649 http://onlinelibrary.wiley.com/doi/10.1002/biot.201600649/abstract
2016.12.02
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Making Graphene Using Laser-induced Phase Separation
IBS & KAIST researchers clarify how laser annealing technology can lead to the production of ultrathin nanomaterials All our smart phones have shiny flat AMOLED (active-matrix organic light-emitting diode) displays. Behind each single pixel of these displays hides at least two silicon transistors which are mass-manufactured using laser annealing technology. While the traditional methods to make the transistors use temperature above 1,000°C, the laser technique reaches the same results at low temperatures even on plastic substrates (melting temperature below 300°C). Interestingly, a similar procedure can be used to generate crystals of graphene. Graphene is a strong and thin nano-material made of carbon, its electric and heat-conductive properties have attracted the attention of scientists worldwide. Professor Keon Jae Lee of the Materials Science and Engineering Department at KAIST and his research group at the Center for Multidimensional Carbon Materials within the Institute for Basic Science (IBS), as well as Professor Sung-Yool Choi of the Electrical Engineering School at KAIST and his research team discovered graphene synthesis mechanism using laser-induced solid-state phase separation of single-crystal silicon carbide (SiC). This study, available in Nature Communications, clarifies how this laser technology can separate a complex compound (SiC) into its ultrathin elements of carbon and silicon. Although several fundamental studies presented the effect of excimer lasers in transforming elemental materials like silicon, the laser interaction with more complex compounds like SiC has rarely been studied due to the complexity of compound phase transition and ultra-short processing time. With high resolution microscope images and molecular dynamic simulations, scientists found that a single-pulse irradiation of xenon chloride excimer laser of 30 nanoseconds melts SiC, leading to the separation of a liquid SiC layer, a disordered carbon layer with graphitic domains (about 2.5 nm thick) on top surface and a polycrystalline silicon layer (about 5 nm) below carbon layer. Giving additional pulses causes the sublimation of the separated silicon, while the disordered carbon layer is transformed into a multilayer graphene. "This research shows that the laser material interaction technology can be a powerful tool for the next generation of two dimensional nanomaterials," said Professor Lee. Professor Choi added: "Using laser-induced phase separation of complex compounds, new types of two dimensional materials can be synthesized in the future." High-resolution transmission electron microscopy shows that after just one laser pulse of 30 nanoseconds, the silicon carbide (SiC) substrate is melted and separates into a carbon and a silicon layer. More pulses cause the carbon layer to organize into graphene and the silicon to leave as gas. Molecular dynamics simulates the graphene formation mechanism. The carbon layer on the top forms because the laser-induced liquid SiC (SiC (l)) is unstable. (Press Release by Courtesy of the Institute for Basic Science (IBS))
2016.12.01
View 11161
Key Interaction between the Circadian Clock and Cancer Identified
Professor Jae Kyoung Kim and his research team from the Department of Mathematical Sciences at KAIST found that the circadian clock drives changes in circadian rhythms of p53 which functions as a tumor suppressor. Using a differential equation, he applied a model-driven mathematical approach to learn the mechanism and role of p53. Kim’s mathematical modeling has been validated by experimental studies conducted by a research team at Virginia Polytechnic Institute and State University (Virginia Tech) in the United State, which is led by Professor Carla Finkielstein. As a result, the researchers revealed that there is an important link existed between the circadian clock and cancer. The findings of this research were published online in Proceedings of the National Academy of Sciences of the United States of the America (PNAS) on November 9, 2016. The circadian clock in our brain controls behavioral and physiological processes within a period of 24 hours, including making us fall asleep at a certain time by triggering the release of the sleep hormone melatonin in our brain, for example, around 9 pm. The clock is also involved in various physiological processes such as cell division, movement, and development. Disruptions caused by the mismatch of the circadian clock and real time due to chronic late night work, shiftwork, and other similar issues may lead to various diseases such as diabetes, cancer, and heart disease. In 2014, when Kim met with Finkielstein, her research team succeeded in observing the changes of p53 over a period of 24 hours, but could not understand how the circadian clock controls the 24-hour rhythm of p53. It was difficult to determine p53’s mechanism since its cell regulation system is far more complex than other cells To solve the problem, Kim set up a computer simulation using mathematical modeling and ran millions of simulations. Instead of the traditional method based on trial and error experiments, mathematical modeling allowed to save a great deal of time, cost, and manpower. During this process, Kim proved that the biorhythm of p53 and Period2, an important protein in the circadian clock, are closely related. Cells usually consist of a cell nucleus and cytoplasm. While p53 exists in both nucleus and cytoplasm, it becomes more stable and its degradation slows down when it is in the nucleus. Kim predicted that the Period2 protein, which plays a key role in the functioning of the circadian clock, could influence the nucleus entry of the p53 protein. Kim’s predictions based on mathematical modeling have been validated by the Virginia team, thereby revealing a strong connection between the circadian clock and cancer. Researchers said that this research will help explain the cause of different results from numerous anticancer drugs, which are used to normalize the level of p53, when they are administrated at different times and find the most effective dosing times for the drugs. They also believe that this study will play an important role in identifying the cause of increasing cancer rates in shift-workers whose circadian clocks are unstable and will contribute to the development of more effective treatments for cancer. Professor Kim said, “This is an exciting thing that my research can contribute to improving the healthy lives of nurses, police officers, firefighters, and the like, who work in shifts against their circadian rhythms. Taking these findings as an opportunity, I hope to see more active interchanges of ideas between biological sciences and mathematical science in Korea.” This research has been jointly conducted between KAIST and Virginia Tech and supported by the T. J. Park Science Fellowship of POSCO, the National Science Foundation of the United States, and the Young Researcher Program of the National Research Foundation of Korea. Picture 1. The complex interaction between tumor antigen p53 and Period2 (Per2) which plays a major role in the circadian clock as revealed by mathematical simulations and experiments Picture 2. A portion of the mathematical model used in the research Picture 3. Professor Jae Kyoung Kim (third from left) and the Virginia Tech Research Team
2016.11.17
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