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An Advanced Method of DNA Nanostructure Formation Developed
Professor Tae-Young Yoon’s research team from the Department of Physics at KAIST has developed a new method to form DNA nanostructures by using magnetic tweezers to observe and to induce the formation of the structure in real time. Unlike traditional designs of "DNA origami" which relies on thermal or chemical annealing methods, the new technology utilizes a completely different dynamic in DNA folding. This allows the folding to be done within only ten minutes. Developed in 2006, the "DNA origami" allows a long skeleton of DNA to be folded into an arbitrary structure by using small stapler DNA pieces. This has been a prominent method in DNA nanotechnology. However, the traditional technology which adopts thermal processes could not control the DNA formation during the folding because every interaction among DNAs occurs simultaneously. Thus, the thermal processes, which take dozens of hours to complete, had to be repeated multiple times in order to find the optimal condition. The research team designed a DNA folding using uni-molecular magnetic tweezers that applied force to a single DNA molecule while measuring the state of the DNA. Through this technology, they were able to induce the formation of DNA nanostructure and observe it at the same time. During high temperature heat treatment, the first stage of conventional thermal processes, the internal structure of the long skeleton DNA untangles. To induce such state, after attaching one side of the skeleton DNA to the surface of glass and the other side to a magnetic material, the team unfolded the internal structure of the DNA by pulling the two sides apart with magnetic force. Unlike the conventional thermal processes, this method lets the stapler DNA swiftly adhere to the skeleton DNA within a minute because the sites are revealed at room temperature. After the stapler pieces connected to the skeleton, the team removed the magnetic force. Next, the structure folded through self-assembly as the stapler DNAs stuck to different sites on the skeleton DNA. Professor Yoon said, “With the existing thermal methods, we could not differentiate the reactions of the DNA because the response of each DNA pieces mutually interacted with each other.” He added that “Using the magnetic tweezers, we were able to sort the process of DNA nanostructure formation into a series of reactions of DNA molecules that are well known, and shorten the time taken for formation in only ten minutes.” He commented, “This nanostructure formation method will enable us to create more intricate and desirable DNA nanostructures by programming the folding of DNA origami structures.” Conducted by Dr. Woori Bae under the guidance of Professor Yoon, the research findings were published online in the December 4th issue of Nature Communications. Figure 1: Uni-molecular magnetic tweezers orchestrating the DNA nanostructure formation Figure 2: The evolution of DNA nanostructure formation using magnetic tweezers. The DNA nanostructure with a 21-nanometer size was formed in about eight minutes.
A Key Signal Transduction Pathway Switch in Cardiomyocyte Identified
A KAIST research team has identified the fundamental principle in deciding the fate of cardiomyocyte or heart muscle cells. They have determined that it depends on the degree of stimulus in β-adrenergic receptor signal transduction pathway in the cardiomyocyte to control cells' survival or death. The findings, the team hopes, can be used to treat various heart diseases including heart failure. The research was led by KAIST Department of Bio and Brain Engineering Chair Professor Kwang-Hyun Cho and conducted by Dr. Sung-Young Shin (lead author) and Ph.D. candidates Ho-Sung Lee and Joon-Hyuk Kang. The research was conducted jointly with GIST (Gwangju Institute of Science and Technology) Department of Biological Sciences Professor Do-Han Kim’s team. The research was supported by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea. The paper was published in Nature Communications on December 17, 2014 with the title, “The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes.” The β-adrenergic receptor signal transduction pathway can promote cell survival (mediated by β2 receptors), but also can result in cell death by inducing toxin (mediated by β1 receptors) that leads to various heart diseases including heart failure. Past attempts to identify the fundamental principle in the fate determining process of cardiomyocyte based on β-adrenergic receptor signalling concluded without much success. The β-adrenergic receptor is a type of protein on the cell membrane of cardiomyocyte (heart muscle cell) that when stimulated by neurohormones such as epinephrine or norepinephrine would transduce signals making the cardiomyocyte contract faster and stronger. The research team used large-scale computer simulation analysis and systems biology to identify ERK* and ICER** signal transduction pathways mediated by a feed-forward circuit as a key molecular switch that decides between cell survival and death. Weak β-adrenergic receptor stimulations activate ERK signal transduction pathway, increasing Bcl-2*** protein expression to promote cardiomyocyte survival. On the other hand, strong β-adrenergic receptor stimulations activate ICER signal transduction pathway, reducing Bcl-2 protein expression to promote cardiomyocyte death. Researchers used a systems biology approach to identify the mechanism of B-blocker****, a common drug prescribed for heart failure. When cardiomyocyte is treated with β1 inhibitor, strong stimulation on β-adrenergic receptor increases Bcl-2 expression, improving the chance of cardiomyocyte survival, a cell protection effect. Professor Kwang-Hyun Cho said, “This research used systems biology, an integrated, convergence research of IT (information technology) and BT (biotechnology), to successfully identify the mechanism in deciding the fate of cardiomyocytes based on the β-adrenergic receptor signal transduction pathway for the first time. I am hopeful that this research will enable the control of cardiomyocyte survival and death to treat various heart diseases including heart failure.” Professor Cho’s team was the first to pioneer a new field of systems biology, especially concerning the complex signal transduction network involved in diseases. Their research is focused on modelling, analyzing simulations, and experimentally proving signal pathways. Professor Cho has published 140 articles in international journals including Cell, Science, and Nature. * ERK (Extracellular signal-regulated kinases): Signal transduction molecule involved in cell survival ** ICER (Inducible cAMP early repressor): Signal transduction molecule involved in cell death *** Bcl-2 (B-cell lymphoma 2): Key signal transduction molecule involved in promotion of cell survival **** β-blocker: Drug that acts as β-adrenergic receptor inhibitor known to slow the progression of heart failure, hence used most commonly in medicine. Picture: A schematic diagram for the β-AR signalling network
Broadband and Ultrathin Polarization Manipulators Developed
Professor Bumki Min from the Department of Mechanical Engineering at KAIST has developed a technology that can manipulate a polarized light in broadband operation with the use of a metamaterial. It is expected that this technology will lead to the development of broadband optical devices that can be applied to broadband communication and display. When an object or its structure is analyzed by using a polarized light such as a laser, the results are generally affected by the polarized state of the light. Therefore, in an optics laboratory, the light is polarized by various methods. In such cases, researchers employ wave plates or photoactive materials. However, the performance of these devices depend vastly on wavelength, and so they are not suitable to be used as a polarizer, especially in broadband. There were many attempts to make artificial materials that are very photoactive by using metamaterials which have a strong resonance. Nonetheless, because the materials had an unavoidable dispersion in the resonance frequency, they were not adequate for broadband operation. Professor Min’s research team arranged and connected helical metamaterials that are smaller than the wavelength of light. They verified theoretically and experimentally that polarized light can be constantly rotated regardless of the wavelength by super-thin materials that have thickness less than one-tenth of the wavelength of the light. The experiment which confirmed the theory was conducted in the microwave band. Broadband polarized rotational 3D metamaterials were found to rotate the polarized microwave within the range of 0.1 GHz to 40 GHz by 45 degrees regardless of its frequency. This nondispersive property is quite unnatural because it is difficult to find a material that does not change in a wide band. In addition, the research team materialized the broadband nondispersive polarized rotational property by designing the metamaterial in a way that it has chirality, which determines the number of rotations proportional to the wavelength. Professor Min said, “As the technology is able to manipulate ultrathin polarization of light in broadband, it will lead to the creation of ultra-shallow broadband optical devices.” Sponsored by the Ministry of Science, ICT and Future Planning of the Republic of Korea and the National Research Foundation of Korea, this research was led by a PhD candidate, Hyun-Sung Park, under the guidance of Professor Min. The research findings were published online in the November 17th issue of Nature Communications. Figure 1 – Broadband and Ultrathin Polarization Manipulators Produced by 3D Printer Figure 2 – Concept of Broadband and Ultrathin Polarization Manipulators
Structure of Neuron-Connecting Synaptic Adhesion Molecules Discovered
A research team has found the three-dimensional structure of synaptic adhesion molecules, which orchestrate synaptogenesis. The research findings also propose the mechanism of synapses in its initial formation. Some brain diseases such as obsessive compulsive disorder (OCD) or bipolar disorders arise from a malfunction of synapses. The team expects the findings to be applied in investigating pathogenesis and developing medicines for such diseases. The research was conducted by a Master’s candidate Kee Hun Kim, Professor Ji Won Um from Yonsei University, and Professor Beom Seok Park from Eulji University under the guidance of Professor Homin Kim from the Graduate School of Medical Science and Engineering, KAIST, and Professor Jaewon Ko from Yonsei University. Sponsored by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, the research findings were published online in the November 14th issue of Nature Communications. A protein that exists in the neuronal transmembrane, Slitrk, interacts with the presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) and forms a protein complex. It is involved in the development of synapses in the initial stage, and balances excitatory and inhibitory signals of neurons. It is known that a disorder in those two proteins cause a malfunction of synapses, resulting in neuropsychosis such as autism, epilepsy, OCD, and bipolar disorders. However, because the structure as well as synaptogenic function of these proteins were not understood, the development of cures could not progress. The research team discovered the three-dimensional structure of two synaptic adhesion molecules like Slitrk and LAR-RPTPs and identified the regions of interaction through protein crystallography and transmission electron microscopy (TEM). Furthermore, they found that the formation of the synapse is induced after the combination of two synaptic adhesion molecules develops a cluster. Professor Kim said, “The research findings will serve as a basis of understanding the pathogenesis of brain diseases which arises from a malfunction of synaptic adhesion molecules. In particular, this is a good example in which collaboration between structural biology and neurobiology has led to a fruitful result.” Professor Ko commented that “this will give new directions to synaptic formation-related-researches by revealing the molecular mechanism of synaptic adhesion molecules.” Figure 1: Overview of the PTPd Ig1–3/Slitrk1 LRR1 complex. Figure 2: Representative negative-stained electron microscopy images of Slitrk1 Full ectodomain (yellow arrows indicate the horseshoe-shaped LRR domains). The typical horseshoe-shaped structures and the randomness of the relative positions of each LRR domain can be observed from the two-dimensional class averages displayed in the orange box. Figure 3: Model of the two-step presynaptic differentiation process mediated by the biding of Slitrks to LAR-RPTPs and subsequent lateral assembly of trans-synaptic LAR-RPTPs/Slitrik complexes.
Professor YongKeun Park Produces Undergraduate Students with International Achievements
Three undergraduate students under the supervision of Professor YongKeun Park from the Department of Physics, KAIST, have published papers in globally renowned academic journals. The most recent publication was made by YoungJu Jo, a senior in physics. Jo’s paper entitled “Angle-resolved light scattering of individual rod-shaped bacteria based on Fourier transform light scattering” was published in the May 28th edition of Scientific Reports. Analyzing bacteria is a very important task in the field of health and food hygiene, but using the conventional biochemical methods of analysis takes days. However, observation with Jo’s newly developed method using light scattering analyzes bacteria within a matter of seconds. SangYeon Cho from the Department of Chemistry also published papers in Cell (2012) and Nature (2013), respectively, under the guidance of Professor Park. SangYeon Cho’s outstanding research achievements were recognized by Harvard and MIT. He was accepted with a full scholarship to Harvard-MIT Health Sciences and Technology Graduate School. He will begin his graduate studies at Harvard-MIT this September. Last March, SeoEun Lee from the Department of Biology was the recipient of the Best Paper Award by the Optical Society of Korea. She plans to pursue a doctoral degree at the College of Physicians and Surgeons, Columbia University in New York. Professor Park said, “Undergraduate students, who are learning a variety of subjects concurrently, are at the most creative time of their lives. KAIST has offered many opportunities to undergraduate students to partake in various research programs.” - Picture (a) and (b): Rod-shaped bacteria’s phase image and light-scattering patterns - Picture (c): Quantitative analysis to illustrate the extraction of information from bacteria
KAIST Top in the Nature Publishing Index 2013 Asia-Pacific
The Nature Publishing Index 2013 Asia-Pacific has been released today. The index is a supplement to Nature, which measures the output of research articles from nations and institutes published in the 18 Nature-branded primary research journals over the calendar year. A press release from the Nature Publishing Group follows below: South Korea regains scientific impetus PRESS RELEASE FROM NATURE PUBLISHING GROUP Embargoed until 03.00 KST on Thursday 27 March 2014 South Korea ranks fourth for scientific research output in the region, according to the Nature Publishing Index 2013 Asia-Pacific released today. In 2013, the nation significantly increased its NPI output following a slight drop in 2012. Named a possible ‘one to watch’ by the supplement editors, with high levels of investment in science and technology announced by both government and private enterprise, its NPI output is growing faster than China’s. The Korea Advanced Institute of Science and Technology has risen two places to take top spot above Seoul National University, which has retained second place. Pohang University of Science and Technology has leapt from eighth to third, with a more-than-threefold increase in corrected count, adjusted for the proportional contribution of collaborative institutions. Last year’s number one, Yonsei University, could not maintain its exceptional 2012 NPI output and has dropped to seventh spot. It is now just above a newcomer, the Institute for Basic Science (IBS), funded as part of the government’s increased investment in basic science. IBS plans to open 50 research centres by 2017 and will no doubt provide increasing contributions in the next few years. To see the latest results for the region, and the Nature Publishing Index Global Top 100, visit the Index website at www.natureasia.com/en/publishing-index. The data posted on the website is updated every week with a moving window of 12 months of data.
Professor Sang-Ouk Kim Publishes Review Article in the Journal of "Nature Materials"
Nature Materials, a peer-reviewed scientific journal published by Nature Publishing Group, covers a range of topics within materials science from materials engineering and structural materials. The journal invited Professor Sang-Ouk Kim of Materials Science and Engineering at KAIST to contribute to the April issue of 2014. Professor Kim, together with his doctoral student, Ju-Young Kim, wrote a review article in the “News and Views” section of the journal, which was entitled “Liquid Crystals: Electric Fields Line Up Graphene Oxide.” The News and Views is a peer-reviewed section where an academic authority in a particular field reviews and evaluates papers published in the journal. In the article, Professor Kim reviewed a paper written by Jang-Kun Song et al. and highlighted important research outcomes such as the efficient electric field switching of graphene oxide (GO) liquid-crystals in low-concentration dispersions and the demonstration of a prototype of a GO liquid-crystal display. This technology could lead the development of a flexible display. Professor Kim is an eminent scholar who has reported for the first time in the world on the solvent-based graphene oxide liquid crystals formation in 2011. For the article, please go to: http://www.kaist.ac.kr/_prog/download.php?filename=Nature_Materials_Professor_Sang-Ouk_Kim_Apr_2014.pdf
A research paper by Professor Myung-Chul Choi reviewed in Science (February 28, 2014)
A research paper entitled “Transformation of taxol-stabilized microtubules into inverted tubulin tubules triggered by a tubulin conformation switch” was published in Nature Materials this year, dated January 19, 2014. Professor Myung-Chul Choi and Dr. Chae-Yeon Song from the Department of Bio and Brain Engineering at KAIST co-authored the paper together with researchers from the University of California in Santa Barbara and the Hebrew University of Jerusalem. Science, dated February 28, 2014, has recently reviewed the paper in its section called "Perspectives."
Spillover Phenomenon Identified Using Model Catalyst System
Researchers at KAIST have identified spillover phenomenon, which has remained controversial since its discovery in the early 1960s. KAIST Department of Chemical and Biomolecular Engineering’s Professor Min-Gi Choi and his team has explained the "spillover phenomenon," using their own model catalyst system where platinum is selectively located within the amorphous aluminosilicate. The research results were published on the 25th February online edition of Nature Communications. Spillover refers to a phenomenon that occurs when hydrogen atoms that have been activated on the surface of metals, such as platinum, move to the surface of the catalyst. It was predicted that this phenomenon can be used to design a catalyst with high activity and stability, and thus has been actively studied over the last 50 years. However, many cases of the known catalysts involved competing reactions on the exposed metal surface, which made it impossible to directly identify the presence and formation mechanism of spillover. The catalysts developed by the researchers at KAIST used platinum nanoparticles covered with aluminosilicate. This only allowed the hydrogen molecules to pass through and has effectively blocked the competing reactions, enabling the research team to study the spillover phenomenon. Through various catalyst structure and reactivity analysis, as well as computer modeling, the team has discovered that Brönsted acid sites present on the aluminosilicate plays a crucial role in spillover phenomenon. In addition, the spillover-based hydrogenation catalyst proposed by the research team showed very high hydrogenation and dehydrogenation activity. The ability of the catalyst to significantly inhibit unwanted hydrogenolysis reaction during the petrochemical processes also suggested a large industrial potential. Professor Min-Gi Choi said, “This particular catalyst, which can trigger the reaction only by spillover phenomenon, can be properly designed to exceed the capacity of the conventional metal catalysts. The future goal is to make a catalyst with much higher activity and selectivity.” The research was conducted through funds subsidized by SK Innovation and Ministry of Science, ICT and Future Planning. The senior research fellow of SK Innovation Seung-Hun Oh said, “SK Innovation will continue to develop a new commercial catalyst based on the technology from this research.” Juh-Wan Lim and Hye-Yeong Shin led the research as joint first authors under supervision of Professor Min-Gi Choi and computer modeling works were conducted by KAIST EEWS (environment, energy, water, and sustainability) graduate school’s Professor Hyeong-Jun Kim.
A Molecular Switch Controlling Self-Assembly of Protein Nanotubes Discovered
International collaborative research among South Korea, United States, and Israel research institutionsThe key to the treatment of cancer and brain disease mechanism The molecular switch that controls the self-assembly structure of the protein nanotubes, which plays crucial role in cell division and intracellular transport of materials, has been discovered. KAIST Bio and Brain Engineering Department’s Professor Myeong-Cheol Choi and Professor Chae-Yeon Song conducted the research, in collaboration with the University of California in Santa Barbara, U.S., and Hebrew University in Israel. The findings of the research were published in Nature Materials on the 19th. Microtubules are tube shaped and composed of protein that plays a key role in cell division, cytoskeleton, and intercellular material transport and is only 25nm in diameter (1/100,000 thickness of a human hair). Conventionally, cancer treatment focused on disrupting the formation of microtubules to suppress the division of cancer cells. In addition Alzheimer’s is known to be caused by the diminishing of structural integrity of microtubules responsible for intercellular material transport which leads to failure in signal transfer. The research team utilized synchrotron x-ray scattering and transmission electron microscope to analyze the self assemble structure of protein nanotubes to subnanometer accuracy. As a result, the microtubules were found to assemble into 25nm thickness tubules by stacking protein blocks 4 x 5 x 8nm in dimension. In the process, the research team discovered the molecular switch that controls the shape of these protein blocks. In addition the research team was successful in creating a new protein tube structure. Professor Choi commented that they were successful in introducing a new paradigm that suggests the possibility of controlling the complex biological functions of human’s biological system with the simple use of physical principles. He commented further that it is anticipated that the findings will allow for the application of bio nanotubes in engineering and that this is a small step in finding the mechanism behind cancer treatment and neural diseases.
Mechanism in regulation of cancer-related key enzyme, ATM, for DNA damage and repair revealed
Professor Kwang-Wook Choi A research team led by Professor Kwang-Wook Choi and Dr. Seong-Tae Hong from the Department of Biological Sciences at KAIST has successfully investigated the operational mechanism of the protein Ataxia Telangiectasia Mutated (ATM), an essential protein to the function of a crucial key enzyme that repairs the damaged DNA which stores biometric information. The results were published on December 19th Nature Communications online edition. All organisms, including humans, constantly strive to protect the information within their DNA from damages posed by a number of factors, such as carbonized materials in our daily food intake, radioactive materials such as radon emitting from the cement of buildings or ultraviolet of the sunlight, which could be a trigger for cancer. In order to keep the DNA information safe, the organisms are always carrying out complex and sophisticated DNA repair work, which involves the crucial DNA damage repair protein ATM. Consequently, a faulty ATM leads to higher risks of cancer. Until now, academia predicted that the Translationally Controlled Tumor Protein (TCTP) will play an important role in regulating the function of ATM. However, since most of main research regarding TCTP has only been conducted in cultured cells, it was unable to identify exactly what mechanisms TCTP employs to control ATM. The KAIST research team identified that TCTP can combine with ATM or increase the enzymatic activity of ATM. In addition, Drosophilia, one of the most widely used model organisms for molecular genetics, has been used to identify that TCTP and ATM play a very important role in repairing the DNA damaged by radiation. This information has allowed the researchers to establish TCTP’s essential function in maintaining the DNA information in cell cultures and even in higher organisms, and to provide specific and important clues to the regulation of ATM by TCTP. Professor Kwang-Wook Choi said, “Our research is a good example that basic research using Drosophilia can make important contributions to understanding the process of diseases, such as cancer, and to developing adequate treatment.” The research has been funded by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea. Figure 1. When the amount of TCTP protein is reduced, cells of the Drosophila's eye are abnormally deformed by radiation. Scale bars = 200mm Figure 2. When the amount of TCTP protein is reduced, the chromosomes of Drosophilia are easily broken by radiation. Scale bars = 10 mm. Figure 3. When gene expressions of TCTP and ATM are reduced, large defects occur in the normal development of the eye. (Left: normal Drosophilia's eye, right: development-deficient eye) Figure 4. ATM marks the position of the broken DNA, with TCTP helping to facilitate this reaction. DNA (blue line) within the cell nucleus is coiled around the histone protein (green cylinder). When DNA is broken, ATM protein attaches a phosphate group (P). Multiple DNA repair protein recognizes the phosphate as a signal that requires repair and gathers at the site.
Ultra-High Strength Metamaterial Developed Using Graphene
New metamaterial has been developed, exhibiting hundreds of times greater strength than pure metals. Professor Seung Min, Han and Yoo Sung, Jeong (Graduate School of Energy, Environment, Water, and Sustainability (EEWS)) and Professor Seok Woo, Jeon (Department of Material Science and Engineering) have developed a composite nanomaterial. The nanomaterial consists of graphene inserted in copper and nickel and exhibits strengths 500 times and 180 times, respectively, greater than that of pure metals. The result of the research was published on the July 2nd online edition in Nature Communications journal. Graphene displays strengths 200 times greater than that of steel, is stretchable, and is flexible. The U.S. Army Armaments Research, Development and Engineering Center developed a graphene-metal nanomaterial but failed to drastically improve the strength of the material. To maximize the strength increased by the addition of graphene, the KAIST research team created a layered structure of metal and graphene. Using CVD (Chemical Vapor Deposition), the team grew a single layer of graphene on a metal deposited substrate and then deposited another metal layer. They repeated this process to produce a metal-graphene multilayer composite material, utilizing a single layer of graphene. Micro-compression tests within Transmission Electronic Microscope and Molecular Dynamics simulations effectively showed the strength enhancing effect and the dislocation movement in grain boundaries of graphene on an atomic level. The mechanical characteristics of the graphene layer within the metal-graphene composite material successfully blocked the dislocations and cracks from external damage from traveling inwards. Therefore the composite material displayed strength beyond conventional metal-metal multilayer materials. The copper-graphene multilayer material with an interplanar distance of 70nm exhibited 500 times greater (1.5GPa) strength than pure copper. Nickel-graphene multilayer material with an interplanar distance of 100nm showed 180 times greater (4.0GPa) strength than pure nickel. It was found that there is a clear relationship between the interplanar distance and the strength of the multilayer material. A smaller interplanar distance made the dislocation movement more difficult and therefore increased the strength of the material. Professor Han, who led the research, commented, “the result is astounding as 0.00004% in weight of graphene increased the strength of the materials by hundreds of times” and “improvements based on this success, especially mass production with roll-to-roll process or metal sintering process in the production of ultra-high strength, lightweight parts for automobile and spacecraft, may become possible.” In addition, Professor Han mentioned that “the new material can be applied to coating materials for nuclear reactor construction or other structural materials requiring high reliability.” The research project received support from National Research Foundation, Global Frontier Program, KAIST EEWS-KINC Program and KISTI Supercomputer and was a collaborative effort with KISTI (Korea Institute of Science and Technology Information), KBSI (Korea Basic Science Institute), Stanford University, and Columbia University. A schematic diagram shows the structure of metal-graphene multi-layers. The metal-graphene multi-layered composite materials, containing a single-layered graphene, block the dislocation movement of graphene layers, resulting in a greater strength in the materials.
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