Receive KAIST news by email!
Type your e-mail address here.
by recently order
by view order
KAIST Research Team Breaks Down Musical Instincts with AI
Music, often referred to as the universal language, is known to be a common component in all cultures. Then, could ‘musical instinct’ be something that is shared to some degree despite the extensive environmental differences amongst cultures? On January 16, a KAIST research team led by Professor Hawoong Jung from the Department of Physics announced to have identified the principle by which musical instincts emerge from the human brain without special learning using an artificial neural network model. Previously, many researchers have attempted to identify the similarities and differences between the music that exist in various different cultures, and tried to understand the origin of the universality. A paper published in Science in 2019 had revealed that music is produced in all ethnographically distinct cultures, and that similar forms of beats and tunes are used. Neuroscientist have also previously found out that a specific part of the human brain, namely the auditory cortex, is responsible for processing musical information. Professor Jung’s team used an artificial neural network model to show that cognitive functions for music forms spontaneously as a result of processing auditory information received from nature, without being taught music. The research team utilized AudioSet, a large-scale collection of sound data provided by Google, and taught the artificial neural network to learn the various sounds. Interestingly, the research team discovered that certain neurons within the network model would respond selectively to music. In other words, they observed the spontaneous generation of neurons that reacted minimally to various other sounds like those of animals, nature, or machines, but showed high levels of response to various forms of music including both instrumental and vocal. The neurons in the artificial neural network model showed similar reactive behaviours to those in the auditory cortex of a real brain. For example, artificial neurons responded less to the sound of music that was cropped into short intervals and were rearranged. This indicates that the spontaneously-generated music-selective neurons encode the temporal structure of music. This property was not limited to a specific genre of music, but emerged across 25 different genres including classic, pop, rock, jazz, and electronic. < Figure 1. Illustration of the musicality of the brain and artificial neural network (created with DALL·E3 AI based on the paper content) > Furthermore, suppressing the activity of the music-selective neurons was found to greatly impede the cognitive accuracy for other natural sounds. That is to say, the neural function that processes musical information helps process other sounds, and that ‘musical ability’ may be an instinct formed as a result of an evolutionary adaptation acquired to better process sounds from nature. Professor Hawoong Jung, who advised the research, said, “The results of our study imply that evolutionary pressure has contributed to forming the universal basis for processing musical information in various cultures.” As for the significance of the research, he explained, “We look forward for this artificially built model with human-like musicality to become an original model for various applications including AI music generation, musical therapy, and for research in musical cognition.” He also commented on its limitations, adding, “This research however does not take into consideration the developmental process that follows the learning of music, and it must be noted that this is a study on the foundation of processing musical information in early development.” < Figure 2. The artificial neural network that learned to recognize non-musical natural sounds in the cyber space distinguishes between music and non-music. > This research, conducted by first author Dr. Gwangsu Kim of the KAIST Department of Physics (current affiliation: MIT Department of Brain and Cognitive Sciences) and Dr. Dong-Kyum Kim (current affiliation: IBS) was published in Nature Communications under the title, “Spontaneous emergence of rudimentary music detectors in deep neural networks”. This research was supported by the National Research Foundation of Korea.
KAIST builds a high-resolution 3D holographic sensor using a single mask
Holographic cameras can provide more realistic images than ordinary cameras thanks to their ability to acquire 3D information about objects. However, existing holographic cameras use interferometers that measure the wavelength and refraction of light through the interference of light waves, which makes them complex and sensitive to their surrounding environment. On August 23, a KAIST research team led by Professor YongKeun Park from the Department of Physics announced a new leap forward in 3D holographic imaging sensor technology. The team proposed an innovative holographic camera technology that does not use complex interferometry. Instead, it uses a mask to precisely measure the phase information of light and reconstruct the 3D information of an object with higher accuracy. < Figure 1. Structure and principle of the proposed holographic camera. The amplitude and phase information of light scattered from a holographic camera can be measured. > The team used a mask that fulfills certain mathematical conditions and incorporated it into an ordinary camera, and the light scattered from a laser is measured through the mask and analyzed using a computer. This does not require a complex interferometer and allows the phase information of light to be collected through a simplified optical system. With this technique, the mask that is placed between the two lenses and behind an object plays an important role. The mask selectively filters specific parts of light,, and the intensity of the light passing through the lens can be measured using an ordinary commercial camera. This technique combines the image data received from the camera with the unique pattern received from the mask and reconstructs an object’s precise 3D information using an algorithm. This method allows a high-resolution 3D image of an object to be captured in any position. In practical situations, one can construct a laser-based holographic 3D image sensor by adding a mask with a simple design to a general image sensor. This makes the design and construction of the optical system much easier. In particular, this novel technology can capture high-resolution holographic images of objects moving at high speeds, which widens its potential field of application. < Figure 2. A moving doll captured by a conventional camera and the proposed holographic camera. When taking a picture without focusing on the object, only a blurred image of the doll can be obtained from a general camera, but the proposed holographic camera can restore the blurred image of the doll into a clear image. > The results of this study, conducted by Dr. Jeonghun Oh from the KAIST Department of Physics as the first author, were published in Nature Communications on August 12 under the title, "Non-interferometric stand-alone single-shot holographic camera using reciprocal diffractive imaging". Dr. Oh said, “The holographic camera module we are suggesting can be built by adding a filter to an ordinary camera, which would allow even non-experts to handle it easily in everyday life if it were to be commercialized.” He added, “In particular, it is a promising candidate with the potential to replace existing remote sensing technologies.” This research was supported by the National Research Foundation’s Leader Research Project, the Korean Ministry of Science and ICT’s Core Hologram Technology Support Project, and the Nano and Material Technology Development Project.
A KAIST research team identifies a cause of mental diseases induced by childhood abuse
Childhood neglect and/or abuse can induce extreme stress that significantly changes neural networks and functions during growth. This can lead to mental illnesses, including depression and schizophrenia, but the exact mechanism and means to control it were yet to be discovered. On August 1, a KAIST research team led by Professor Won-Suk Chung from the Department of Biological Sciences announced the identification of excessive synapse removal mediated by astrocytes as the cause of mental diseases induced by childhood abuse trauma. Their research was published in Immunity, a top international journal in the field of immunology. The research team discovered that the excessive astrocyte-mediated removal of excitatory synapses in the brain in response to stress hormones is a cause of mental diseases induced by childhood neglect and abuse. Clinical data have previously shown that high levels of stress can lead to various mental diseases, but the exact mechanism has been unknown. The results of this research therefore are expected to be widely applied to the prevention and treatment of such diseases. The research team clinically screened an FDA-approved drug to uncover the mechanism that regulates the phagocytotic role of astrocytes, in which they capture external substances and eliminate them. As a result, the team found that synthetic glucocorticoids, namely stress hormones, enhanced astrocyte-mediated phagocytosis to an abnormal level. Glucocorticoids play essential roles in processes that maintain life, such as carbohydrate metabolism and anti-inflammation, but are also secreted in response to external stimuli such as stress, allowing the body to respond appropriately. However, excessive and long-term exposure to glucocorticoids caused by chronic stress can lead to various mental diseases including depression, cognitive disorders, and anxiety. < Figure 1. Results of screening for compounds that increase astrocyte phagocytosis (A) Discovered that synthetic glucocorticoid (stress hormone) increases the phagocytosis of astrocytes through screening of FDA-approved clinical compounds. (B-C) When treated with stress hormones, the phagocytosis of astrocytes is greatly increased, but this phenomenon is strongly suppressed by the GR antagonist (Mifepristone). CORT: corticosterone (stress hormone), Eplerenone: mineralocorticoid receptor (MR) antagonist, Mifepristone: glucocorticoid receptor (GR) antagonist > To understand the changes in astrocyte functions caused by childhood stress, the research team used mice models with early social deprivation, and discovered that stress hormones bind to the glucocorticoid receptors (GRs) of astrocytes. This significantly increased the expression of Mer tyrosine kinase (MERK), which plays an essential role in astrocyte phagocytosis. Surprisingly, out of the various neurons in the cerebral cortex, astrocytes would eliminate only the excitatory synapses of specific neurons. The team found that this builds abnormal neural networks, which can lead to complex behavioral abnormalities such as social deficiencies and depression in adulthood. The team also observed that microglia, which also play an important role in cerebral immunity, did not contribute to synapse removal in the mice models with early social deprivation. This confirms that the response to stress hormones during childhood is specifically astrocyte-mediated. To find out whether these results are also applicable in humans, the research team used a brain organoid grown from human-induced pluripotent stem cells to observe human responses to stress hormones. The team observed that the stress hormones induced astrocyte GRs and phagocyte activation in the human brain organoid as well, and confirmed that the astrocytes subsequently eliminated excessive amounts of excitatory synapses. By showing that mice and humans both showed the same synapse control mechanism in response to stress, the team suggested that this discovery is applicable to mental disorders in humans. < Figure 2. A schematic diagram of the study published in Immunity. Excessive stress hormone secretion in childhood increases the expression of the MERTK phagocytic receptor through the glucocorticoid receptor (GR) of astrocytes, resulting in excessive elimination of excitatory synapses. Excessive synaptic elimination by astrocytes during brain development causes permanent damage to brain circuits, resulting in abnormal neural activity in the adult brain and psychiatric behaviors such as depression and anti-social tendencies. > Prof. Won-Suk Chung said, “Until now, we did not know the exact mechanism for how childhood stress caused brain diseases. This research was the first to show that the excessive phagocytosis of astrocytes could be an important cause of such diseases.” He added, “In the future, controlling the immune response of astrocytes will be used as a fundamental target for understanding and treating brain diseases.” This research, written by co-first authors Youkyeong Byun (Ph.D. candidate) and Nam-Shik Kim (post-doctoral associate) from the KAIST Department of Biological Sciences, was published in the internationally renowned journal Immunity, a sister magazine of Cell and one of the best journal in the field of immunology, on July 31 under the title "Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis." This work was supported by a National Research Foundation of Korea grant, the Korea Health Industry Development Institute (KHIDI), and the Korea Dementia Research Center (KDRC).
KAIST research team develops a forgery prevention technique using salmon DNA
The authenticity scandal that plagued the artwork “Beautiful Woman” by Kyung-ja Chun for 30 years shows how concerns about replicas can become a burden to artists, as most of them are not experts in the field of anti-counterfeiting. To solve this problem, artist-friendly physical unclonable functions (PUFs) based on optical techniques instead of electronic ones, which can be applied immediately onto artwork through brushstrokes are needed. On May 23, a KAIST research team led by Professor Dong Ki Yoon in the Department of Chemistry revealed the development of a proprietary technology for security and certification using random patterns that occur during the self-assembly of soft materials. With the development of the Internet of Things in recent years, various electronic devices and services can now be connected to the internet and carry out new innovative functions. However, counterfeiting technologies that infringe on individuals’ privacy have also entered the marketplace. The technique developed by the research team involves random and spontaneous patterns that naturally occur during the self-assembly of two different types of soft materials, which can be used in the same way as human fingerprints for non-replicable security. This is very significant in that even non-experts in the field of security can construct anti-counterfeiting systems through simple actions like drawing a picture. The team developed two unique methods. The first method uses liquid crystals. When liquid crystals become trapped in patterned substrates, they induce the symmetrical destruction of the structure and create a maze-like topology (Figure 1). The research team defined the pathways open to the right as 0 (blue), and those open to the left as 1 (red), and confirmed that the structure could be converted into a digital code composed of 0’s and 1’s that can serve as a type of fingerprint through object recognition using machine learning. This groundbreaking technique can be utilized by non-experts, as it does not require complex semiconductor patterns that are required by existing technology, and can be observed through the level of resolution of a smartphone camera. In particular, this technique can reconstruct information more easily than conventional methods that use semiconductor chips. < Figure 1. Security technology using the maze made up of magnetically-assembled structures formed on a substrate patterned with liquid crystal materials. > The second method uses DNA extracted from salmon. The DNA can be dissolved in water and applied with a brush to induce bulking instability, which forms random patterns similar to a zebra’s stripes. Here, the patterns create ridge endings and bifurcation, which are characteristics in fingerprints, and these can also be digitalized into 0’s and 1’s through machine learning. The research team applied conventional fingerprint recognition technology to this patterning technique and demonstrated its use as an artificial fingerprint. This method can be easily carried out using a brush, and the solution can be mixed into various colors and used as a new security ink. < Figure 2. Technology to produce security ink using DNA polymers extracted from salmon > This new security technology developed by the research team uses only simple organic materials and requires basic manufacturing processes, making it possible to enhance security at a low cost. In addition, users can produce patterns in the shapes and sizes they want, and even if the patterns are made in the same way, their randomness makes each individual pattern different. This provides high levels of security and gives the technique enhanced marketability. Professor Dong Ki Yoon said, “These studies have taken the randomness that naturally occurs during self-assembly to create non-replicable patterns that can act like human fingerprints.” He added, “These ideas will be the cornerstone of technology that applies the many randomities that exist in nature to security systems.” The two studies were published in the journal Advanced Materials under the titles “1Planar Spin Glass with Topologically-Protected Mazes in the Liquid Crystal Targeting for Reconfigurable Micro Security Media” and “2Paintable Physical Unclonable Function Using DNA” on May 6 and 5, respectively. Author Information: 1Geonhyeong Park, Yun-Seok Choi, S. Joon Kwon*, and Dong Ki Yoon*/ 2Soon Mo Park†, Geonhyeong Park†, Dong Ki Yoon*: †co-first authors, *corresponding author This research was funded by the Center for Multiscale Chiral Architectures and supported by the Ministry of Science and ICT-Korea Research Foundation, BRIDGE Convergent Research and Development Program, the Running Together Project, and the Samsung Future Technology Development Program. < Figure 1-1. A scene from the schematic animation of the process of Blues (0) and Reds (1) forming the PUF by exploring the maze. From "Planar Spin Glass with Topologically-Protected Mazes in the Liquid Crystal Targeting for Reconfigurable Micro Security Media" by Geonhyeong Park, Yun-Seok Choi, S. Joon Kwon, Dong Ki Yoon. https://doi.org/10.1002/adma.202303077 > < Figure 2-1. A schematic diagram of the formation of digital fingerprints formed using the DNA ink. From "Paintable Physical Unclonable Function Using DNA" by Soon Mo Park, Geonhyeong Park, Dong Ki Yoon. https://doi.org/10.1002/adma.202302135 >
KAIST researchers find the key to overcome the limits in X-ray microscopy
X-ray microscopes have the advantage of penetrating most substances, so internal organs and skeletons can be observed non-invasively through chest X-rays or CT scans. Recently, studies to increase the resolution of X-ray imaging technology are being actively conducted in order to precisely observe the internal structure of semiconductors and batteries at the nanoscale. KAIST (President Kwang Hyung Lee) announced on April 12th that a joint research team led by Professor YongKeun Park of the Department of Physics and Dr. Jun Lim of the Pohang Accelerator Laboratory has succeeded in developing a core technology that can overcome the resolution limitations of existing X-ray microscopes. d This study, in which Dr. KyeoReh Lee participated as the first author, was published on 6th of April in “Light: Science and Application”, a world-renowned academic journal in optics and photonics. (Paper title: Direct high-resolution X-ray imaging exploiting pseudorandomness). X-ray nanomicroscopes do not have refractive lenses. In an X-ray microscope, a circular grating called a concentric zone plate is used instead of a lens. The resolution of an image obtained using the zone plate is determined by the quality of the nanostructure that comprises the plate. There are several difficulties in fabricating and maintaining these nanostructures, which set the limit to the level of resolution for X-ray microscopy. The research team developed a new X-ray nanomicroscopy technology to overcome this problem. The X-ray lens proposed by the research team is in the form of numerous holes punched in a thin tungsten film, and generates random diffraction patterns by diffracting incident X-rays. The research team mathematically identified that, paradoxically, the high-resolution information of the sample was fully contained in these random diffraction patterns, and actually succeeded in extracting the information and imaging the internal states of the samples. The imaging method using the mathematical properties of random diffraction was proposed and implemented in the visible light band for the first time by Dr. KyeoReh Lee and Professor YongKeun Park in 2016*. This study uses the results of previous studies to solve the difficult, lingering problem in the field of the X-ray imaging. ※ "Exploiting the speckle-correlation scattering matrix for a compact reference-free holographic image sensor." Nature communications 7.1 (2016): 13359. The resolution of the image of the constructed sample has no direct correlation with the size of the pattern etched on the random lens used. Based on this idea, the research team succeeded in acquiring images with 14 nm resolution (approximately 1/7 the size of the coronavirus) by using random lenses made in a circular pattern with a diameter of 300 nm. The imaging technology developed by this research team is a key fundamental technology that can enhance the resolution of X-ray nanomicroscopy, which has been blocked by limitations of the production of existing zone plates. The first author and one of the co-corresponding author, Dr. KyeoReh Lee of KAIST Department of Physics, said, “In this study, the resolution was limited to 14 nm, but if the next-generation X-ray light source and high-performance X-ray detector are used, the resolution would exceed that of the conventional X-ray nano-imaging and approach the resolution of an electron microscope.” and added, “Unlike an electron microscope, X-rays can observe the internal structure without damaging the sample, so it will be able to present a new standard for non-invasive nanostructure observation processes such as quality inspections for semiconductors.”. The co-corresponding author, Dr. Jun Lim of the Pohang Accelerator Laboratory, said, “In the same context, the developed image technology is expected to greatly increase the performance in the 4th generation multipurpose radiation accelerator which is set to be established in Ochang of the Northern Chungcheong Province.” This research was conducted with the support through the Research Leader Program and the Sejong Science Fellowship of the National Research Foundation of Korea. Fig. 1. Designed diffuser as X-ray imaging lens. a, Schematic of full-field transmission X-ray microscopy. The attenuation (amplitude) map of a sample is measured. The image resolution (dx) is limited by the outermost zone width of the zone plate (D). b, Schematic of the proposed method. A designed diffuser is used instead of a zone plate. The image resolution is finer than the hole size of the diffuser (dx << D). Fig. 2. The left panel is a surface electron microscopy (SEM) image of the X-ray diffuser used in the experiment. The middle panel shows the design of the X-ray diffuser, and there is an inset in the middle of the panel that shows a corresponding part of the SEM image. The right panel shows an experimental random X-ray diffraction pattern, also known as a speckle pattern, obtained from the X-ray diffuser. Fig. 3. Images taken from the proposed randomness-based X-ray imaging (bottom) and the corresponding surface electron microscope (SEM) images (top).
KAIST research team develops a cheap and safe redox flow battery
Redox flow batteries, one of the potential replacements for the widely used lithium-ion secondary batteries, can be utilized as new and renewable energy as well as for energy storage systems (ESS) thanks to their low cost, low flammability, and long lifetime of over 20 years. Since the price of vanadium, the most widely used active material for redox flow batteries, has been rising in recent years, scientists have been actively searching for redox materials to replace it. On March 23, a joint research team led by Professors Hye Ryung Byon and Mu-Hyun Baik from the KAIST Department of Chemistry, and Professor Jongcheol Seo from the POSTECH Department of Chemistry announced that they had developed a highly soluble and stable organic redox-active molecule for use in aqueous redox flow batteries. The research team focused on developing aqueous redox flow batteries by redesigning an organic molecule. It is possible to control the solubility and electrochemical redox potential of organic molecules by engineering their design, which makes them a promising active material candidate with possibly higher energy storage capabilities than vanadium. Most organic redox-active molecules have low solubilities or have slow chemical stability during redox reactions. Low solubility means low energy storage capacity and low chemical stability leads to reduced cycle performance. For this research, the team chose naphthalene diimide (NDI) as their active molecule. Until now, there was little research done on NDI despite its high chemical stability, as it shows low solubility in aqueous electrolyte solutions. Although NDI molecules are almost insoluble in water, the research team tethered four ammonium functionalities and achieved a solubility as high as 1.5M* in water. In addition, they confirmed that when a 1M solution of NDI was used in neutral redox flow batteries for 500 cycles, 98% of its capacity was maintained. This means 0.004% capacity decay per cycle, and only 2% of its capacity would be lost if the battery were to be operated for 45 days. Furthermore, the developed NDI molecule can save two electrons per molecule, and the team proved that 2M of electrons could be stored in every 1M of NDI solution used. For reference, vanadium used in vanadium redox flow batteries, which require a highly concentrated sulfuric acid solution, has a solubility of about 1.6M and can only hold one electron per molecule, meaning it can store a total of 1.6M of electrons. Therefore, the newly developed NDI active molecule shows a higher storage capacity compared to existing vanadium devices. *1M (mol/L): 6.022 x 1023 active molecules are present in 1L of solution This paper, written by co-first authors Research Professor Vikram Singh, and Ph.D. candidates Seongyeon Kwon and Yunseop Choi, was published in the online version of Advanced Materials on February 7 under the title, Controlling π-π interactions of highly soluble naphthalene diimide derivatives for neutral pH aqueous redox flow batteries. Ph.D. Candidate Yelim Yi and Professor Mi Hee Lee’s team from the KAIST Department of Chemistry also contributed to the study by conducting electron paramagnetic resonance analyses. Professor Hye Ryung Byon said, “We have demonstrated the principles of molecular design by modifying an existing organic active molecule with low solubility and utilizing it as an active molecule for redox flow batteries. We have also shown that during a redox reaction, we can use molecular interactions to suppress the chemical reactivity of radically formed molecules.” She added, “Should this be used later for aqueous redox flow batteries, along with its high energy density and high solubility, it would also have the advantage of being available for use in neutral pH electrolytes. Vanadium redox flow batteries currently use acidic solutions, which cause corrosion, and we expect our molecule to solve this issue. Since existing lithium ion-based ESS are flammable, we must develop safer and cheaper next-generation ESS, and our research has shown great promise in addressing this.” This research was funded by Samsung Research Funding & Incubation Center, the Institute for Basic Science, and the National Research Foundation. Figure 1. (a) Structures of various NDI molecules. (b) Solubility of NDI molecules in water (black bars) and aqueous electrolytes including KCl electrolyte (blue bars). (c–d) Structural changes of the molecules as the developed NDI molecule stores two electrons. (c) Illustration of cluster combination and separation of NDI molecules developed during redox reaction and (d) Snapshot of the MD simulation. NDI molecules prepared from the left, formation of bimolecular sieve and tetramolecular sieve clusters after the first reductive reaction, and a single molecule with a three-dimensional structure after the second reduction. Figure 2. Performance results of an aqueous redox flow battery using 1M of the developed NDI molecule as the cathode electrolyte and 3.1M of ammonium iodine as the anode electrolyte. Using 1.5 M KCl solution. (a) A schematic diagram of a redox flow battery. (b) Voltage-capacity graph according to cycle in a redox flow battery. (c) Graphs of capacity and coulombs, voltage, and energy efficiency maintained at 500 cycles.
Using light to throw and catch atoms to open up a new chapter for quantum computing
The technology to move and arrange atoms, the most basic component of a quantum computer, is very important to Rydberg quantum computing research. However, to place the atoms at the desired location, the atoms must be captured and transported one by one using a highly focused laser beam, commonly referred to as an optical tweezer. and, the quantum information of the atoms is likely to change midway. KAIST (President Kwang Hyung Lee) announced on the 27th that a research team led by Professor Jaewook Ahn of the Department of Physics developed a technology to throw and receive rubidium atoms one by one using a laser beam. The research team developed a method to throw and receive atoms which would minimize the time the optical tweezers are in contact with the atoms in which the quantum information the atoms carry may change. The research team used the characteristic that the rubidium atoms, which are kept at a very low temperature of 40μK below absolute zero, move very sensitively to the electromagnetic force applied by light along the focal point of the light tweezers. The research team accelerated the laser of an optical tweezer to give an optical kick to an atom to send it to a target, then caught the flying atom with another optical tweezer to stop it. The atom flew at a speed of 65 cm/s, and traveled up to 4.2 μm. Compared to the existing technique of guiding the atoms with the optical tweezers, the technique of throwing and receiving atoms eliminates the need to calculate the transporting path for the tweezers, and makes it easier to fix the defects in the atomic arrangement. As a result, it is effective in generating and maintaining a large number of atomic arrangements, and when the technology is used to throw and receive flying atom qubits, it will be used in studying new and more powerful quantum computing methods that presupposes the structural changes in quantum arrangements. "This technology will be used to develop larger and more powerful Rydberg quantum computers," says Professor Jaewook Ahn. “In a Rydberg quantum computer,” he continues, “atoms are arranged to store quantum information and interact with neighboring atoms through electromagnetic forces to perform quantum computing. The method of throwing an atom away for quick reconstruction the quantum array can be an effective way to fix an error in a quantum computer that requires a removal or replacement of an atom.” The research, which was conducted by doctoral students Hansub Hwang and Andrew Byun of the Department of Physics at KAIST and Sylvain de Léséleuc, a researcher at the National Institute of Natural Sciences in Japan, was published in the international journal, Optica, 0n March 9th. (Paper title: Optical tweezers throw and catch single atoms). This research was carried out with the support of the Samsung Science & Technology Foundation. <Figure 1> A schematic diagram of the atom catching and throwing technique. The optical tweezer on the left kicks the atom to throw it into a trajectory to have the tweezer on the right catch it to stop it.
KAIST research team develops clathrin assembly for targeted protein delivery to cancer cells
In order to effectively treat cancer without additional side effects, we need a way to deliver drugs specifically to tumor cells. Protein assemblies have been widely used for drug delivery in the field of cancer treatment, but to use them for drug delivery they must first be functionalized, meaning they must be bound to the protein that recognizes the target tumor cell and deliver a drug that kills it. However, the functionalization process of protein assemblies is very complex, inefficient, and limited to small-sized chemical drugs, which limits their real-life applicability. On March 14, a KAIST research team led by Professor Hak-Sung Kim from the KAIST Department of Biological Sciences reported the development of a clathrin assembly that can specifically deliver drugs to cancer cells. Clathrin assemblies transport materials efficiently through endocytosis in living organisms. They are formed by the self-assembly of triskelion units, which are composed of three heavy chains bonded with three light chains. Inspired by this mechanism, the research team designed a clathrin chain to facilitate the functionalization of tumor cell recognition proteins and toxin proteins in order to deliver drugs specifically to tumor cells. From this, the team created a new type of clathrin assembly. Figure 1. (Upper) Schematic diagram of the development of a new clathrin assembly that simultaneously functionalizes two types of proteins (cancer cell recognition protein and toxin protein) on heavy and light chains of clathrin in a one-pot reaction (bottom, left) Electron microscopy image of clathrin assembly: formation of an assembly with a diameter of about 28 nanometers (bottom, right) Cancer cell killing effect of CLA: CLA functionalized with epidermal growth factor receptor (EGFR) recognition protein and toxin protein kills only the cancer cells that overexpress EGFR. The newly developed clathrin assembly requires a one-pot reaction, meaning both the toxin and tumor-recognition proteins can be functionalized simultaneously and show high efficiency. As a result, this technique is expected to be used in a wide variety of applications in the fields of biology and medicine including drug delivery, vaccine development, and diagnosing illnesses. In this research, an epidermal growth factor receptor (EGFR), a common tumor marker, was used as the recognition protein, allowing drug delivery only to tumor cells. The clathrin assemblies that were functionalized to recognize EGFR showed a bonding strength 900-times stronger than it normally would due to the avidity effect. Based on this finding, the research team confirmed that treatment with toxin-functionalized clathrin assembly led to effective cell death for tumor cells, while it showed no such effect on healthy cells. This research by Dr. Hong-Sik Kim and his colleagues was published in Small volume 19, issue 8 on February 22 under the title, "Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery", and it was selected as the cover paper. Figure 2. Cover Paper: This study was published in the international journal 'Small' on February 22nd, Volume 19, No. 8, and was selected as the cover paper. First author Dr. Hong-Sik Kim said, “Clathrin is difficult to functionalize, and since it is extracted from mammals, realistic applications have been limited.” He added, “But the new clathrin assembly we designed for this research can be functionalized with two different types of proteins through a single-step reaction, and can be produced from E. coli, meaning it can become an applicable protein assembly technology for a wide range of biomedical fields.” This research was funded by the Global Ph.D. Fellowship and the Mid-career Researcher Grant of the National Research Foundation.
KAIST researchers develops a tech to enable production of ultrahigh-resolution LED with sub-micrometer scale pixels
Ultrahigh-resolution displays are an essential element for developing next-generation electronic products such as virtual reality (VR), augmented reality (AR), and smart watches, and can be applied not only to head-mounted displays, but also to smart glasses and smart lenses. The technology developed through this research is expected to be used to make such next-generation ultrahigh-resolution displays and other various sub-micro optoelectronic devices. KAIST (President Kwang Hyung Lee) announced on the 22nd that Professor Yong-Hoon Cho's research team of KAIST Department of Physics developed the core technology for an ultrahigh resolution light-emitting diode (LED) display that can realize 0.5 micron-scale pixels smaller than 1/100 of the average hair thickness (about 100 microns) using focused ion beams. Commonly, pixelation of ultrahigh-resolution LED displays usually relies on the etching method that physically cuts the area around the pixel, but as the pixel becomes smaller due to the occurrence of various defects around it, leading to side-effects of having leakage of current increased and light-emission efficiency decreased. In addition, various complex processes such as patterning for pixelation and post-processing for prevention of leakage current are required. Professor Yong-Hoon Cho's research team developed a technology that can create pixels down to the size of a microscale without the complicated pre- and post-processing using a focused ion beam. This method has the advantage of being able to freely set the shape of the emitting pixel without causing any structural deformation on the material surface by controlling the intensity of the focused ion beam. The focused ion beam technology has been widely used for ultrahigh-magnification imaging and nanostructure fabrication in fields such as materials engineering and biology. However, when a focused ion beam is used on a light emitting body such as an LED, light emission of a portion hit by the beam and a surrounding area rapidly decreases, which has been a barrier to fabricating a nano-scale light emitting structure. Upon facing this issue, Professor Cho's research team began the research on the idea that if they turned things around to use these problematic phenomena, they can be used in ultra-fine pixelation method on a sub-micron scale. The research team used a focused ion beam whose intensity was softened to the extent that the surface was not shaved, and found that not only the light-emission rapidly decreased in the area hit by the focused ion beam, but also the local resistance greatly increased. As a result, while the surface of the LED is kept flat, the portion hit by the focused ion beam is optically and electrically isolated, enabling pixelation for independent operation. Professor Yong-Hoon Cho, who led the research, said, “We have newly developed a technology that can create sub-micron-scale pixels without complicated processes using a focused ion beam, which will be a base technology that can be applied to next-generation ultrahigh-resolution displays and nano-photoelectronic devices.” This research in which the Master's student Ji-Hwan Moon and the Ph.D. student Baul Kim of KAIST Department of Physics participated as co-first authors, was carried out with the support of the National Research Foundation of Korea's Support Program for Mid-Career Researchers and the Institute of Information and Communications Technology Planning and Evaluation. It was published online in 'Advanced Materials' on February 13, and was also selected as the internal cover of the next offline edition. (Title: Electrically Driven Sub-Micron Light-Emitting Diode Arrays Using Maskless and Etching-Free Pixelation) Figure 1. Schematic diagram of the technology for ultrahigh density sub-micron-sized pixels through He focused ion beam (FIB) irradiation on an LED device Figure 2. Ultra-high-density pixelation technology of micro light-emitting diodes (μLED) through He focused ion beam (FIB) irradiation Figure 3. Rectangular pixels of different sizes (surface structure picture and luminescence picture) realized by a focused ion beam. Luminescence pictures of pixel arrays ranging in size from 20 µm x 20 µm to 0.5 µm x 0.5 µm, with surface flatness maintained.
Afternoon chemotherapy proved to deliver more desirable results for female lymphoma patients
Chemotherapy is a commonly used regimen for cancer treatment, but it is also a double-edged sword. While the drugs are highly effective at killing cancer cells, they are also notorious for killing healthy cells in the body. As such, minimizing the drug’s damage to the patient’s body is necessary for improving the prognosis of chemotherapy. Recently, “chrono-chemotherapy” have been gaining interest in the research community. As the name suggests, the aim is timing the delivery of the drugs when the body is least vulnerable to their harmful effects and while the cancer cells are at their most vulnerable. < Figure 1. Chrono-chemotherapy considering circadian rhythm > Chrono-chemotherapy exploits the fact that human physiological processes, including cell proliferation and differentiation, are regulated by an endogenous timer called the circadian clock. However, this has not been widely exploited in real-world clinical settings because, as of now, there is no systematic method for finding the optimal chemotherapy delivery time. This problem was tackled by an interdisciplinary team of researchers from South Korea. They were led by principal investigators Jae Kyoung Kim (a mathematician from the Biomedical Mathematics Group, Institute for Basic Science) and Youngil Koh (an oncologist at Seoul National University Hospital). The researchers studied a group of patients suffering from diffuse large B-cell lymphoma (DLBCL). Terminology * Diffuse large B-cell lymphoma (DLBCL): Lymphoma is a type of blood cancer caused by the malignant transformation of lymphoid tissue cells. Lymphoma is divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma (malignant lymphoma), and diffuse large B-cell lymphoma accounts for about 30 to 40% of non-Hodgkin's lymphoma. The research team noticed that DLBCL patients at Seoul National University Hospital received chemotherapy on two different schedules, with some patients receiving morning treatment (8:30 a.m.) and others taking the drugs in the afternoon (2:30 p.m.). All patients received the same cancer treatment (R-CHOP), which is a combination of targeted therapy and chemotherapy, four to six times in the morning or afternoon at intervals of about three weeks. They analyzed 210 patients to investigate whether there was any difference between morning and afternoon treatments. It was found that female patients who received the afternoon treatment had a 12.5 times reduced mortality rate (25% to 2%), while the cancer recurrence after 60 months decreased by 2.8 times (37% to 13%). In addition, chemotherapy side effects such as neutropenia were more common in female patients who received the morning treatment. Surprisingly, there was no differences found in treatment efficiency depending on the treatment schedule in the cases of male patients. To understand the cause of the gender differences, the research team analyzed upto 14,000 blood samples from the Seoul National University Hospital Health Examination Center. It was found that in females, white blood cell counts tended to decrease in the morning and increase in the afternoon. This indicates that the bone marrow proliferation rate was higher in the morning than in the afternoon because there is a upto 12 hour delay between bone marrow proliferation and blood cell production. This means that if a female patient receives chemotherapy in the morning when bone marrow is actively producing blood cells, the possibility of adverse side effects becomes greater. These results are consistent with the findings from recent randomized clinical trials that showed female colorectal cancer patients treated with irinotecan in the morning suffered from higher drug toxicities. One confounding variable was the drug dose. Since the morning female patients suffered from greater adverse side effects, oftentimes the dose had to be reduced for these patients. On average, the drug dose was reduced by upto 10% compared to the dose intensity given to female patients receiving the afternoon treatment. Unlike the female patients, it was found that male patients did not show a significant difference in white blood cell count and bone marrow cell proliferation activity throughout the day, which explains why the timing of the treatment had no impact. Professor Youngil Koh said, “We plan to verify the conclusions of this study again with a large-scale follow-up study that completely controls for the confounding variables, and to confirm whether chrono-chemotherapy has similar effects on other cancers.” CI Jae Kyoung Kim said, “Because the time of the internal circadian clock can vary greatly depending on the individual's sleep-wake patterns, we are currently developing a technology to estimate a patient’s circadian clock from their sleep pattern. We hope that this can be used to develop an individualized anti-cancer chronotherapy schedule.” < Figure 2. Chemotherapy in the afternoon can improve treatment outcomes. > The daily fluctuation of proliferative activity of bone marrow is larger in females than in males, and it becomes higher in the morning (left). Thus, chemotherapy in the morning strongly inhibits proliferative activity in female lymphoma patients, resulting in a higher incidence of adverse events such as neutropenia and infections. This forced the clinicians to reduce the dose intensity (center). Consequently, female patients undergoing the morning treatment showed a lower survival probability than those undergoing the afternoon treatment (right). Specifically, only ~13% of female patients treated in the afternoon had a worse outcome and ~2% of them died while ~37% of female patients treated in the morning had a worse outcome and ~25% of them died. Male patients did not show any difference in treatment outcomes depending on the chemotherapy delivery time.
Scientists re-writes FDA-recommended equation to improve estimation of drug-drug interaction
Drugs absorbed into the body are metabolized and thus removed by enzymes from several organs like the liver. How fast a drug is cleared out of the system can be affected by other drugs that are taken together because added substance can increase the amount of enzyme secretion in the body. This dramatically decreases the concentration of a drug, reducing its efficacy, often leading to the failure of having any effect at all. Therefore, accurately predicting the clearance rate in the presence of drug-drug interaction* is critical in the process of drug prescription and development of a new drug in order to ensure its efficacy and/or to avoid unwanted side-effects. *Drug-drug interaction: In terms of metabolism, drug-drug interaction is a phenomenon in which one drug changes the metabolism of another drug to promote or inhibit its excretion from the body when two or more drugs are taken together. As a result, it increases the toxicity of medicines or causes loss of efficacy. Since it is practically impossible to evaluate all interactions between new drug candidates and all marketed drugs during the development process, the FDA recommends indirect evaluation of drug interactions using a formula suggested in their guidance, first published in 1997, revised in January of 2020, in order to evaluate drug interactions and minimize side effects of having to use more than one type of drugs at once. The formula relies on the 110-year-old Michaelis-Menten (MM) model, which has a fundamental limit of making a very broad and groundless assumption on the part of the presence of the enzymes that metabolizes the drug. While MM equation has been one of the most widely known equations in biochemistry used in more than 220,000 published papers, the MM equation is accurate only when the concentration of the enzyme that metabolizes the drug is almost non-existent, causing the accuracy of the equation highly unsatisfactory – only 38 percent of the predictions had less than two-fold errors. “To make up for the gap, researcher resorted to plugging in scientifically unjustified constants into the equation,” Professor Jung-woo Chae of Chungnam National University College of Pharmacy said. “This is comparable to having to have the epicyclic orbits introduced to explain the motion of the planets back in the days in order to explain the now-defunct Ptolemaic theory, because it was 'THE' theory back then.” < (From left) Ph.D. student Yun Min Song (KAIST, co-first authors), Professor Sang Kyum Kim (Chungnam National University, co-corresponding author), Jae Kyoung Kim, CI (KAIST, co-corresponding author), Professor Jung-woo Chae (Chungnam National University, co-corresponding author), Ph.D. students Quyen Thi Tran and Ngoc-Anh Thi Vu (Chungnam National University, co-first authors) > A joint research team composed of mathematicians from the Biomedical Mathematics Group within the Institute for Basic Science (IBS) and the Korea Advanced Institute of Science and Technology (KAIST) and pharmacological scientists from the Chungnam National University reported that they identified the major causes of the FDA-recommended equation’s inaccuracies and presented a solution. When estimating the gut bioavailability (Fg), which is the key parameter of the equation, the fraction absorbed from the gut lumen (Fa) is usually assumed to be 1. However, many experiments have shown that Fa is less than 1, obviously since it can’t be expected that all of the orally taken drugs to be completely absorbed by the intestines. To solve this problem, the research team used an “estimated Fa” value based on factors such as the drug’s transit time, intestine radius, and permeability values and used it to re-calculate Fg. Also, taking a different approach from the MM equation, the team used an alternative model they derived in a previous study back in 2020, which can more accurately predict the drug metabolism rate regardless of the enzyme concentration. Combining these changes, the modified equation with re-calculated Fg had a dramatically increased accuracy of the resulting estimate. The existing FDA formula predicted drug interactions within a 2-fold margin of error at the rate of 38%, whereas the accuracy rate of the revised formula reached 80%. “Such drastic improvement in drug-drug interaction prediction accuracy is expected to make great contribution to increasing the success rate of new drug development and drug efficacy in clinical trials. As the results of this study were published in one of the top clinical pharmacology journal, it is expected that the FDA guidance will be revised according to the results of this study.” said Professor Sang Kyum Kim from Chungnam National University College of Pharmacy. Furthermore, this study highlights the importance of collaborative research between research groups in vastly different disciplines, in a field that is as dynamic as drug interactions. “Thanks to the collaborative research between mathematics and pharmacy, we were able to recify the formula that we have accepted to be the right answer for so long to finally grasp on the leads toward healthier life for mankind.,” said Professor Jae Kyung Kim. He continued, “I hope seeing a ‘K-formula’ entered into the US FDA guidance one day.” The results of this study were published in the online edition of Clinical Pharmacology and Therapeutics (IF 7.051), an authoritative journal in the field of clinical pharmacology, on December 15, 2022 (Korean time). Thesis Title: Beyond the Michaelis-Menten: Accurate Prediction of Drug Interactions through Cytochrome P450 3A4 Induction (doi: 10.1002/cpt.2824) < Figure 1. The formula proposed by the FDA guidance for predicting drug-drug interactions (top) and the formula newly derived by the researchers (bottom). AUCR (the ratio of substrate area under the plasma concentration-time curve) represents the rate of change in drug concentration due to drug interactions. The research team more than doubled the accuracy of drug interaction prediction compared to the existing formula. > < Figure 2. Existing FDA formulas tend to underestimate the extent of drug-drug interactions (gray dots) than the actual measured values. On the other hand, the newly derived equation (red dot) has a prediction rate that is within the error range of 2 times (0.5 to 2 times) of the measured value, and is more than twice as high as the existing equation. The solid line in the figure represents the predicted value that matches the measured value. The dotted line represents the predicted value with an error of 0.5 to 2 times. > For further information or to request media assistance, please contact Jae Kyoung Kim at Biomedical Mathematics Group, Institute for Basic Science (IBS) (firstname.lastname@example.org) or William I. Suh at the IBS Communications Team (email@example.com). - About the Institute for Basic Science (IBS) IBS was founded in 2011 by the government of the Republic of Korea with the sole purpose of driving forward the development of basic science in South Korea. IBS has 4 research institutes and 33 research centers as of January 2023. There are eleven physics, three mathematics, five chemistry, nine life science, two earth science, and three interdisciplinary research centers.
KAIST Research Team Proves How a Neurotransmitter may be the Key in Controlling Alzheimer’s Toxicity
With nearly 50 million dementia patients worldwide, and Alzheimers’s disease is the most common neurodegenerative disease. Its main symptom is the impairment of general cognitive abilities, including the ability to speak or to remember. The importance of finding a cure is widely understood with increasingly aging population and the life expectancy being ever-extended. However, even the cause of the grim disease is yet to be given a clear definition. A KAIST research team in the Department of Chemistry led by professor Mi Hee Lim took on a lead to discovered a new role for somatostatin, a protein-based neurotransmitter, in reducing the toxicity caused in the pathogenic mechanism taken towards development of Alzheimer’s disease. The study was published in the July issue of Nature Chemistry under the title, “Conformational and functional changes of the native neuropeptide somatostatin occur in the presence of copper and amyloid-β”. According to the amyloid hypothesis, the abnormal deposition of Aβ proteins causes death of neuronal cells. While Aβ agglomerations make up most of the aged plaques through fibrosis, in recent studies, high concentrations of transitional metal were found in the plaques from Alzheimer’s patients. This suggests a close interaction between metallic ions and Aβ, which accelerates the fibrosis of proteins. Copper in particular is a redox-activating transition metal that can produce large amounts of oxygen and cause serious oxidative stress on cell organelles. Aβ proteins and transition metals can closely interact with neurotransmitters at synapses, but the direct effects of such abnormalities on the structure and function of neurotransmitters are yet to be understood. Figure 1. Functional shift of somatostatin (SST) by factors in the pathogenesis of Alzheimer's disease. Figure 2. Somatostatin’s loss-of-function as neurotransmitter. a. Schematic diagram of SST auto-aggregation due to Alzheimer's pathological factors. b. SST’s aggregation by copper ions. c. Coordination-prediction structure and N-terminal folding of copper-SST. d. Inhibition of SST receptor binding specificity by metals. In their research, Professor Lim’s team discovered that when somatostatin, the protein-based neurotransmitter, is met with copper, Aβ, and metal-Aβ complexes, self-aggregates and ceases to perform its innate function of transmitting neural signals, but begins to attenuate the toxicity and agglomeration of metal-Aβ complexes. Figure 3. Gain-of-function of somatostatin (SST) in the dementia setting. a. Prediction of docking of SST and amyloid beta. b. SST making metal-amyloid beta aggregates into an amorphous form. c. Cytotoxic mitigation effect of SST. d. SST mitigating the interaction between amyloid beta protein with the cell membrane. This research, by Dr. Jiyeon Han et al. from the KAIST Department of Chemistry, revealed the coordination structure between copper and somatostatin at a molecular level through which it suggested the agglomeration mechanism, and discovered the effects of somatostatin on Aβ agglomeration path depending on the presence or absence of metals. The team has further confirmed somatostatin’s receptor binding, interactions with cell membranes, and effects on cell toxicity for the first time to receive international attention. Professor Mi Hee Lim said, “This research has great significance in having discovered a new role of neurotransmitters in the pathogenesis of Alzheimer’s disease.” “We expect this research to contribute to defining the pathogenic network of neurodegenerative diseases caused by aging, and to the development of future biomarkers and medicine,” she added. This research was conducted jointly by Professor Seung-Hee Lee’s team of KAIST Department of Biological Sciences, Professor Kiyoung Park’s Team of KAIST Department of Chemistry, and Professor Yulong Li’s team of Peking University. The research was funded by Basic Science Research Program of the National Research Foundation of Korea and KAIST. For more information about the research team, visit the website: https://sites.google.com/site/miheelimlab/1-professor-mi-hee-lim.
마지막 페이지 8
KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
Copyright(C) 2020, Korea Advanced Institute of Science and Technology,
All Rights Reserved.