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Newly Identified Meningeal Lymphatic Vessels Answers the Key Questions on Brain Clearance
(Figure: Schematic images of location and features of meningeal lymphatic vessels and their changes associated with ageing.) Just see what happens when your neighborhood’s waste disposal system is out of service. Not only do the piles of trash stink but they can indeed hinder the area’s normal functioning. That is also the case when the brain’s waste management is on the blink. The buildup of toxic proteins in the brain causes a massive damage to the nerves, leading to cognitive dysfunction and increased probability of developing neurodegenerative disorders such as Alzheimer's disease. Though the brain drains its waste via the cerebrospinal fluid (CSF), little has been understood about an accurate route for the brain’s cleansing mechanism. Medical scientists led by Professor Gou Young Koh at the Graduate School of Medical Science and Engineering have reported the basal side of the skull as the major route, so called “hotspot” for CSF drainage. They found that basal meningeal lymphatic vessels (mLVs) function as the main plumbing pipes for CSF. They confirmed macromolecules in the CSF mainly runs through the basal mLVs. Notably, the team also revealed that the brain’s major drainage system, specifically basal mLVs are impaired with aging. Their findings have been reported in the journal Nature on July 24. Throughout our body, excess fluids and waste products are removed from tissues via lymphatic vessels. It was only recently discovered that the brain also has a lymphatic drainage system. mLVs are supposed to carry waste from the brain tissue fluid and the CSF down the deep cervical lymph nodes for disposal. Still scientist are left with one perplexing question — where is the main exit for the CSF? Though mLVs in the upper part of the skull (dorsal meningeal lymphatic vessels) were reported as the brain’s clearance pathways in 2014, no substantial drainage mechanism was observed in that section. “As a hidden exit for CSF, we looked into the mLVs trapped within complex structures at the base of the skull,” says Dr. Ji Hoon Ahn, the first author of this study. The researchers used several techniques to characterize the basal mLVs in detail. They used a genetically engineered lymphatic-reporter mouse model to visualize mLVs under a fluorescence microscope. By performing a careful examination of the mice skull, they found distinctive features of basal mLVs that make them suitable for CSF uptake and drainage. Just like typical functional lymphatic vessels, basal mLVs are found to have abundant lymphatic vessel branches with finger-like protrusions. Additionally, valves inside the basal mLVs allow the flow to go in one direction. In particular, they found that the basal mLVs are closely located to the CSF. Dr. Hyunsoo Cho, the first author of this study explains, “All up, it seemed a solid case that basal mLVs are the brain’s main clearance pathways. The researchers verified such specialized morphologic characteristics of basal mLVs indeed facilitate the CSF uptake and drainage. Using CSF contrast-enhanced magnetic resonance imaging in a rat model, they found that CSF is drained preferentially through the basal mLVs. They also utilized a lymphatic-reporter mouse model and discovered that fluorescence-tagged tracer injected into the brain itself or the CSF is cleared mainly through the basal mLVs. Jun-Hee Kim, the first author of this study notes, “We literally saw that the brain clearance mechanism utilizing basal outflow route to exit the skull. It has long been suggested that CSF turnover and drainage declines with ageing. However, alteration of mLVs associated with ageing is poorly understood. In this study, the researchers observed changes of mLVs in young (3-month-old) and aged (24~27-months-old) mice. They found that the structure of the basal mLVs and their lymphatic valves in aged mice become severely flawed, thus hampering CSF clearance. The corresponding author of this study, Dr. Koh says, “By characterizing the precise route for fluids leaving the brain, this study improves our understanding on how waste is cleared from the brain. Our findings also provide further insights into the role of impaired CSF clearance in the development of age-related neurodegenerative diseases.” Many current therapies for Alzheimer’s disease target abnormally accumulated proteins, such as beta-amyloid. By mapping out a precise route for the brain’s waste clearance system, this study may be able to help find ways to improve the brain’s cleansing function. Such breakthrough might become quite a sensational strategy for eliminating the buildup of aging-related toxic proteins. “It definitely warrants more extensive investigation of mLVs in patients with age-related neurodegenerative disease such as Alzheimer’s disease prior to clinical investigation,” adds Professor Koh.
Deciphering Brain Somatic Mutations Associated with Alzheimer's Disease
Researchers have found a potential link between non-inherited somatic mutations in the brain and the progression of Alzheimer’s disease Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer’s disease (AD). Their findings were published in the journal Nature Communications last week. Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear. Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing. The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) – mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases. The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD. Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient’s brain. They found the mutation was 4.9 time more abundant in AT8-positive – a marker for hyper-phosphorylated tau proteins– neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins. “Our study provides new insights into the molecular genetic factors behind Alzheimer’s disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain,” said Professor Lee. The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer’s disease. (Figure 1. Bioinformatic pipeline for detecting low-level brain somatic mutations in AD and non-AD.) (Figure 2. Pathogenic brain somatic mutations associated with tau phosphorylation are significantly enriched in AD brains.) (Figure 3. A pathogenic brain somatic mutation in PIN1 (c. 477 C>T) is a loss-of-function and related functional assays show its haploinsufficiency increases phosphorylation and aggregation of tau.)
Efficiently Producing Fatty Acids and Biofuels from Glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production. The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates. Fossil fuels, which have long been energy resources for our daily lives, are now facing serious challenges: depletion of their reserves and their role in global warming. The production of sustainable bio-based renewable energy has emerged as an essential alternative and many studies to replace fossil fuels are underway. One of the representative examples is biodiesel. Currently, it is mainly being produced through the transesterification of vegetable oils or animal fats. The research team engineered oleaginous microorganisms, Rhodococcus opacus, to produce fatty acids and their derivatives that can be used as biodiesel from glucose, one of the most abundant and cheap sugars derived from non-edible biomass. Professor Lee’s team has already engineered Escherichia coli to produce short-chain hydrocarbons, which can be used as gasoline (published in Nature as the cover paper in 2013). However, the production efficiency of the short-chain hydrocarbons using E. coli (0.58 g/L) fell short of the levels required for commercialization. To overcome these issues, the team employed oil-accumulating Rhodococcus opacus as a host strain in this study. First, the team optimized the cultivation conditions of Rhodococcus opacus to maximize the accumulation of oil (triacylglycerol), which serves as a precursor for the biosynthesis of fatty acids and their derivatives. Then, they systematically analyzed the metabolism of the strain and redesigned it to enable higher levels of fatty acids and two kinds of fatty acid-derived biodiesels (fatty acid ethyl esters and long-chain hydrocarbons) to be produced. They found that the resulting strains produced 50.2, 21.3, and 5.2 g/L of fatty acids, fatty acid ethyl esters, and long-chain hydrocarbons, respectively. These are all the highest concentrations ever reported by microbial fermentations. It is expected that these strains can contribute to the future industrialization of microbial-based biodiesel production. “This technology creates fatty acids and biodiesel with high efficiency by utilizing lignocellulose, one of the most abundant resources on the Earth, without depending on fossil fuels and vegetable or animal oils. This will provide new opportunities for oil and petroleum industries, which have long relied on fossil fuels, to turn to sustainable and eco-friendly biotechnologies,” said Professor Lee. This paper titled “Engineering of an oleaginous bacterium for the production of fatty acids and fuels” was published in Nature Chemical Biology on June 17. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557). (Figure: Metabolic engineering for the production of free fatty acids (FFAs), fatty acid ethyl esters (FAEEs), and long-chain hydrocarbons (LCHCs) in Rhodococcus opacus PD630. Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.) # # # Source: Hye Mi Kim, Tong Un Chae, So Young Choi, Won Jun Kim and Sang Yup Lee. Engineering of an oleaginous bacterium for the production of fatty acids and fuels. Nature Chemical Biology ( https://www.nature.com/nchembio/ ) DOI: 10.1038/s41589-019-0295-5 Profile Dr. Sang Yup Lee firstname.lastname@example.org Distinguished Professor at the Department of Chemical and Biomolecular Engineering KAIST
Real-Time Analysis of MOF Adsorption Behavior
Researchers have developed a technology to analyze the adsorption behavior of molecules in each individual pore of a metal organic framework (MOF). This system has large specific surface areas, allowing for the real-time observation of the adsorption process of an MOF, a new material effective for sorting carbon dioxide, hydrogen, and methane. Accurate measurements and assessments of gas adsorption isotherms are important for characterizing porous materials and developing their applications. The existing technology is only able to measure the amount of gas molecules adsorbed to the material, without directly observing the adsorption behavior. The research team led by Professor Jeung Ku Kang from the Graduate School of Energy, Environment, Water and Sustainability (EEWS) prescribed a real time gas adsorption crystallography system by integrating an existing X-ray diffraction (XRD) measurement device that can provide structural information and a gas adsorption measurement device. Specifically, the system allowed the observation of a mesoporous MOF that has multiple pores rather than a single pore structure. The research team categorized the adsorption behaviors of MOF molecules by pore type, followed by observations and measurements, resulting in the identification of a stepwise adsorption process that was previously not possible to analyze. Further, the team systematically and quantitatively analyzed how the pore structure and the type of adsorption molecule affect the adsorption behavior to suggest what type of MOF structure is appropriate as a storage material for each type of adsorption behavior. Professor Kang said, “We quantitatively analyzed each pore molecule in real time to identify the effects of chemical and structural properties of pores on adsorption behavior.” He continued, “By understanding the real-time adsorption behavior of molecules at the level of the pores that form the material, rather than the whole material, we will be able to apply this technology to develop a new high-capacity storage material.” This research was published in Nature Chemistry online on May 13, 2019 under the title ‘Isotherms of Individual Pores by Gas Adsorption Crystallography’. (Figure. Schematic illustration of molecules adsorbed on metal organic frameworks with different pores of various structures, where the In-situ X-ray crystallography has been developed to classify each pore structure and analyze the position of the molecule to determine the amount of molecules adsorbed to each pore.)
Novel Via-Hole-Less Multilevel Metal Interconnection Methods
Forming reliable multi-level metal interconnections is a key technology for integrating devices into organic integrated circuits (ICs). The conventional approach, called “via-hole,” locally removes the insulator and utilizes metal interconnects through the holes. Due to the high sensitivity of organic materials to chemical solvents, heat, and photo-radiation used in conventional “via-hole” methods, alternative printing methods or laser drilling methods have been developed. However, finding a reliable and practical metal interconnection for organic ICs is still challenging. The research team of KAIST Professor Sung Gap Im and Postech Professor Kim Jae-Joon reported a new interconnection method that does not require via-hole formation, “via-hole-less metal interconnection,” in Nature Communications on June 3. Metal electrodes in different layers can be isolated from each other by patterned dielectric layers, where they then can be interconnected to others in the open area where the dielectric layer is not present. See the images below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below. Professor Kim explained, “Our proposed via-hole-less interconnect method using a selectively patterned dielectric overcomes the limitations of the previous time-consuming, one-by-one via-hole formation process and provides reliable methods for creating metal interconnects in organic ICs. We expect the via-hole-less scheme to bring advances to organic IC technology.”
A Hole in One for Holographic Display
(Professor YongKeun Park) Researchers have designed an ultrathin display that can project dynamic, multi-coloured, 3D holographic images, according to a study published in Nature Communications. The system’s critical component is a thin film of titanium filled with tiny holes that precisely correspond with each pixel in a liquid crystal display (LCD) panel. This film acts as a ‘photon sieve’ – each pinhole diffracts light emerging from them widely, resulting in a high-definition 3D image observable from a wide angle. The entire system is very small: they used a 1.8-inch off-the-shelf LCD panel with a resolution of 1024 x 768. The titanium film, attached to the back of the panel, is a mere 300 nanometres thick. “Our approach suggests that holographic displays could be projected from thin devices, like a cell phone,” says Professor YongKeun Park, a physicist at KAIST who led the research. The team demonstrated their approach by producing a hologram of a moving, tri-coloured cube. Specifically, the images are made by pointing differently coloured laser beams made of parallel light rays at the small LCD panel. The photon sieve has a hole for each pixel in the LCD panel. The holes are precisely positioned to correspond to the pixel’s active area. The pinholes diffract the light emerging from them, producing 3D images. Previous studies from Professor Park’s group have used optical diffusors for the same purpose, but the size of the device was bulky and difficult to be operated, and it took a long period of time to calibrate. In the present work, on the other hand, the group tailored their photon sieve to demonstrate a simple, compact and scalable method for 3D holographic display. This technique can be readily applied to existing LCD displays. Applications for holograms have been limited by cumbersome techniques, high computation requirements, and poor image quality. Improving current techniques could lead to a wide variety of applications, including 3D cinema viewing without the need for glasses, watching holographic videos on television and smart phone screens. Figure 1. The actual 3D holographic display, and an electron microscope image of the non-periodic pinholes. Figure 2. Three-dimensional dynamic color hologram operating at 60 Hz
Unravelling Inherent Electrocatalysis to Improve the Performance of Hydrogen Fuel Cells
(Figure 1. Electrode structure for the precise evaluation of the metal nanoparticles’ electrochemical catalytic characteristics at a high temperature.) A KAIST team presented an ideal electrode design to enhance the performance of high-temperature fuel cells. The new analytical platform with advanced nanoscale patterning method quantitatively revealed the electrochemical value of metal nanoparticles dispersed on the oxide electrode, thus leading to electrode design directions that can be used in a variety of eco-friendly energy technologies. The team, working under Professor WooChul Jung and Professor Sang Ouk Kim at the Department of Materials Science and Engineering, described an accurate analysis of the reactivity of oxide electrodes boosted by metal nanoparticles, where all particles participate in the reaction. They identified how the metal catalysts activate hydrogen electro-oxidation on the ceria-based electrode surface and quantify how rapidly the reaction rate increases with the proper choice of metals. Metal nanoparticles with diameters of 10 nanometers or less have become a key component in high-performance heterogeneous catalysts, primarily serving as a catalytic activator. Recent experimental and theoretical findings suggest that the optimization of the chemical nature at the metal and support interfaces is essential for performance improvement. However, the high cost associated with cell fabrication and operation as well as poorer stability of metal nanoparticles at high temperatures have been a long-standing challenge. To solve this problem, the team utilized a globally recognized metal nano patterning technology that uses block copolymer self-assembled nano templates and succeeded in uniformly synthesizing metal particles 10 nanometers in size on the surface of oxide fuel cell electrodes. They also developed a technology to accurately analyze the catalyst characteristics of single particles at high temperatures and maximize the performance of a fuel cell with minimal catalyst use. The research team confirmed that platinum, which is a commonly used metal catalyst, could boost fuel cell performance by as much as 21 times even at an amount of 300 nanograms, which only costs about 0.015 KRW. The team quantitatively identified and compared the characteristics of widely used metal catalysts other than platinum, such as palladium, gold, and cobalt, and also elucidated the precise principle of catalyst performance through theoretical analysis. (Figure 2. Comparison of the electrochemical catalytic characteristics for various 10nm metal nanoparticles (platinum, palladium, cobalt, gold) at a high temperature.) Professor Jung said, "We have broken the conventional methods of increasing the amount of catalyst which have deemed inefficient and expensive. Our results suggest a clear idea for high performance fuel cells using very small amounts of nanoparticles. This technology can be applied to many different industrial fields, advancing the commercialization of eco-friendly energy technologies such as fuel cells that generate electricity and electrolytic cells that produce hydrogen from water.” The research has been published as the cover article of Nature Nanotechnology in the March issue. This research was carried out with support from the Nano-Material Technology Development Program through the National Research Foundation of Korea.
Blue-enriched White Light to Wake You Up in the Morning
(from left: Professor Hyun Jung Chung, Professor Hyeon-Jeong Suk, Taesu Kim and Professor Kyungah Choi) Here is a good news for those of who have difficulty with morning alertness. A KAIST research team proposed that a blue-enriched LED light can effectively help people overcome morning drowsiness. This study will provide the basis for major changes in future lighting strategies and thereby help create better indoor environments. Considerable research has been devoted to unmasking circadian rhythms. The 2017 Nobel Prize in Physiology or Medicine went to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for unveiling the molecular mechanisms that control circadian rhythms. In particular, the relationship between light and its physiological effects has been investigated since the discovery of a novel, third type of photoreceptor in the human retina in the early 2000s. Rods and cones regulate visual effects, while the third type, photosensitive retinal ganglion cells, regulate a large variety of biological and behavioral processes including melatonin and cortisol secretion, alertness, and functional magnetic resonance imaging (fMRI). Initial studies on light sources have shown that blue monochromatic, fully saturated lights are effective for stimulating physiological responses, but the relative effectiveness of commercially available white light sources is less well understood. Moreover, the research was more focused on the negative effects of blue light; for instance, when people are exposed to blue light at night, they have trouble achieving deep sleep because the light restrains melatonin secretion. However, Professor Hyeon-Jeong Suk and Professor Kyungah Choi from the Department of Industrial Design and their team argue that the effects of blue-enriched morning light on physiological responses are time dependent, and that it has positive effects on melatonin levels and the subjective perception of alertness, mood, and visual comfort compared with warm white light. The team conducted an experiment with 15 university students. They investigated whether an hour of morning light exposure with different chromaticity would affect their physiological and subjective responses differently. The decline of melatonin levels was significantly greater after the exposure to blue-enriched white light in comparison with warm white light. Professor Suk said, “Light takes a huge part of our lives since we spend most of our time indoors. Light is one of the most powerful tools to affect changes in how we perceive and experience the environment around us.” Professor Choi added, “When we investigate all of the psychological and physiological effects of light, we see there is much more to light than just efficient quantities. I believe that human-centric lighting strategies could be applied to a variety of environments, including residential areas, learning environments, and working spaces to improve our everyday lives.” This research was collaborated with Professor Hyun Jung Chung from the Graduate School of Nanoscience and Technology and was published in Scientific Reports (10.1038/s41598-018-36791-5) on January 23, 2019. Figure 1. Changes in melatonin secretion during day and night time
New Catalyst for Synthesizing Chiral Molecules Selectively
(from left: Dr. Yoonsu Park and Professor Sukbok Chang from the Department of Chemistry) Molecules in nature often have “twin” molecules that look identical. In particular, the twin molecules that look like mirror images to each other are called enantiomers. However, even though they have the same type and number of elements, these twin molecules exhibit completely different properties. Professor Sukbok Chang and Dr. Yoonsu Park from the Department of Chemistry developed a new catalyst capable of selectively synthesizing only one of the two enantiomers. Using this catalyst, the have succeeded in manufacturing the chiral lactam, an essential ingredient in pharmaceuticals, from a hydrocarbon compound. Enantiomerism or chirality is considered very important for drug development. Biomaterials, such as DNAs and proteins also have chiral properties, but they exhibit different physiological activities depending on the types of drugs. One type of the enantiomer could be useful while the other is toxic. Hence, the technology for selective synthesizing (i.e. asymmetric synthesis) is required, but it is still regarded as a great challenge faced by modern chemistry to date. The researchers solved this problem by developing a new catalyst. Earlier they presented their research on developing an iridium catalyst that converts hydrocarbons into high value γ-lactam compounds, and published it in Science in March 2018. However, the developed catalyst still had a limitation that both types of enantiomers are obtained without selectivity. In this study, they found that among dozens of other catalyst candidates, iridium catalysts with chiral diamine scaffolds were able to select the correct enantiomer with a selectivity of 99% or more. This novel catalyst can be used to synthesize the various chiral γ-lactam as required. A left-handed γ-lactam and a right-handed γ-lactam can be produced using a left-handed iridium catalyst and a right-handed iridium catalyst, respectively. They analyzed the reason for the high selectivity through computational chemistry simulations. They identified that temporal hydrogen bonding occurred between the chiral diamine catalysts and the hydrocarbon compound during the reaction. As a result of the hydrogen bonding, the formation of the left-handed lactam was boosted. With their new catalyst, they also succeeded in synthesizing chiral lactam compounds with different structures. By using inexpensive and readily available feedstock hydrocarbons, the researchers produced a group of chiral lactams in different shapes. As their chirality and diverse structures enable lactams to function as an active compound in the body for antibiotic, anti-inflammatory, or anti-tumoral functions, this study may facilitate the development of potential drugs in a more efficient and cheaper way. Professor Chang said, “We hope that our research on selectively producing core units of effective drugs will lead to developing new drugs that demonstrate fewer side-effects and higher efficacy. There are also economic advantages of this research because it uses hydrocarbon compounds, which can be abundantly found in nature, to produce high-value raw materials. This research was published in Nature Catalysis(10.1038/s41929-019-0230-x) on February 19, 2019. Figure 1. Asymmetric formation of chiral γ-lactam Figure 2. Outline of research outcome
New LSB with Theoretical Capacity over 90%
(Professor Hee-Tak Kim and Hyunwon Chu) A KAIST research team has developed a lithium sulfur battery (LSB) that realizes 92% of the theoretical capacity and an areal capacity of 4mAh/cm2. LSBs are gaining a great deal of attention as an alternative for lithium ion batteries (LIBs) because they have a theoretical energy density up to six to seven times higher than that of LIBs, and can be manufactured in a more cost-effective way. However, LSBs face the obstacle of having a capacity reaching its theoretical maximum because they are prone to uncontrolled growth of lithium sulfide on the electrodes, which leads to blocking electron transfer. To address the problem of electrode passivation, researchers introduced additional conductive agent into the electrode; however, it drastically lowered the energy density of LSBs, making it difficult to exceed 70% of the theoretical capacity. Professor Hee-Tak Kim from the Department of Chemical and Biomolecular Engineering and his team replaced the lithium salt anions used in conventional LSB electrolytes with anions with a high donor number. The team successfully induced the three-dimensional growth of lithium sulfide on electrode surfaces and efficiently delayed the electrode passivation. Based on this electrolyte design, the research team achieved 92% of the theoretical capacity with their high-capacity sulfur electrode (4mAh/cm2), which is equivalent to that of conventional LIB cathode. Furthermore, they were able to form a stable passivation film on the surface of the lithium anode and exhibited stable operation over 100 cycles. This technology, which can be flexibly used with various types of sulfur electrodes, can mark a new milestone in the battery industry. Professor Kim said, “We proposed a new physiochemical principle to overcome the limitations of conventional LSBs. I believe our achievement of obtaining 90% of the LBSs’ theoretical capacity without any capacity loss after 100 cycles will become a new milestone.” This research, first-authored by Hyunwon Chu and Hyungjun Noh, was published in Nature Communications on January 14, 2019. It was also selected in the editor’s highlight for its outstanding achievements. Figure 1. Lithium sulfur growth and its deposition mechanism for different sulfide growth behaviors Figure 2. Capacity and cycle life characteristics of the LSBs
Noninvasive Light-Sensitive Recombinase for Deep Brain Genetic Manipulation
A KAIST team presented a noninvasive light-sensitive photoactivatable recombinase suitable for genetic manipulation in vivo. The highly light-sensitive property of photoactivatable Flp recombinase will be ideal for controlling genetic manipulation in deep mouse brain regions by illumination with a noninvasive light-emitting diode. This easy-to-use optogenetic module made by Professor Won Do Heo and his team will provide a side-effect free and expandable genetic manipulation tool for neuroscience research. Spatiotemporal control of gene expression has been acclaimed as a valuable strategy for identifying functions of genes with complex neural circuits. Studies of complex brain functions require highly sophisticated and robust technologies that enable specific labeling and rapid genetic modification in live animals. A number of approaches for controlling the activity of proteins or expression of genes in a spatiotemporal manner using light, small molecules, hormones, and peptides have been developed for manipulating intact circuits or functions. Among them, recombination-employing, chemically inducible systems are the most commonly used in vivo gene-modification systems. Other approaches include selective or conditional Cre-activation systems within subsets of green fluorescent protein-expressing cells or dual-promoter-driven intersectional populations of cells. However, these methods are limited by the considerable time and effort required to establish knock-in mouse lines and by constraints on spatiotemporal control, which relies on a limited set of available genetic promoters and transgenic mouse resources. Beyond these constraints, optogenetic approaches allow the activity of genetically defined neurons in the mouse brain to be controlled with high spatiotemporal resolution. However, an optogenetic module for gene-manipulation capable of revealing the spatiotemporal functions of specific target genes in the mouse brain has remained a challenge. In the study published at Nature Communication on Jan. 18, the team featured photoactivatable Flp recombinase by searching out split sites of Flp recombinase that were not previously identified, being capable of reconstitution to be active. The team validated the highly light-sensitive, efficient performance of photoactivatable Flp recombinase through precise light targeting by showing transgene expression within anatomically confined mouse brain regions. The concept of local genetic labeling presented here suggests a new approach for genetically identifying subpopulations of cells defined by the spatial and temporal characteristics of light delivery. To date, an optogenetic module for gene-manipulation capable of revealing spatiotemporal functions of specific target genes in the mouse brain has remained out of reach and no such light-inducible Flp system has been developed. Accordingly, the team sought to develop a photoactivatable Flp recombinase that takes full advantage of the high spatiotemporal control offered by light stimulation. This activation through noninvasive light illumination deep inside the brain is advantageous in that it avoids chemical or optic fiber implantation-mediated side effects, such as off-target cytotoxicity or physical lesions that might influence animal physiology or behaviors. The technique provides expandable utilities for transgene expression systems upon Flp recombinase activity in vivo, by designing a viral vector for minimal leaky expression influenced by viral nascent promoters. The team demonstrated the utility of PA-Flp as a noninvasive in vivo optogenetic manipulation tool for use in the mouse brain, even applicable for deep brain structures as it can reach the hippocampus or medial septum using external LED light illumination. The study is the result of five years of research by Professor Heo, who has led the bio-imaging and optogenetics fields by developing his own bio-imaging and optogenetics technologies. “It will be a great advantage to control specific gene expression desired by LEDs with little physical and chemical stimulation that can affect the physiological phenomenon in living animals,” he explained.
Technology to Control Near-Field Thermal Radiation
(from left clockwise: Professor Seung Seob Lee, Professor Bong Jae Lee, PhD Mikyung Lim and PhD candidate Jaeman Song) A KAIST research team succeeded in measuring and controlling the near-field thermal radiation between metallo-dielectric (MD) multilayer structures. Their thermal radiation control technology can be applied to next-generation semiconductor packaging, thermophotovoltaic cells and thermal management systems. It also has the potential to be applied to a sustainable energy source for IoT sensors. In the nanoscale gaps, thermal radiation between objects increases greatly with closer distances. The amount of heat transfer in this scale was found to be from 1,000 to 10,000 times greater than the blackbody radiation heat transfer, which was once considered the theoretical maximum for the rate of thermal radiation. This phenomenon is called near-field thermal radiation. With recent developments in nanotechnology, research into near-field thermal radiation between various materials has been actively carried out. Surface polariton coupling generated from nanostructures has been of particular interest because it enhances the amount of near-field thermal radiation between two objects, and allows the spectral control of near-field thermal radiation. This advantage has motivated much of the recent theoretical research on the application of near-field thermal radiation using nanostructures, such as thin films, multilayer nanostructures, and nanowires. Nevertheless, thus far, most of the studies have focused on measuring near-field thermal radiation between isotropic materials. A joint team led by Professor Bong Jae Lee and Professor Seung Seob Lee from the Department of Mechanical Engineering succeeded in measuring near-field thermal radiation according to the vacuum distance between MD multilayer nanostructures by using a custom MEMS (Micro-Electro-Mechanical Systems)-device-integrated platform with three-axis nanopositioner. MD multilayer nanostructures refer to structures in which metal and dielectric layers with regular thickness alternate. The MD single-layer pair is referred to as a unit cell, and the ratio of the thickness occupied by the metal layer in the unit cell is called the fill factor. By measuring the near-field thermal radiation with a varying number of unit cells and the fill factor of the multilayer nanostructures, the team demonstrated that the surface plasmon polariton coupling enhances near-field thermal radiation greatly, and allows spectral control over the heat transfer. Professor B. J. Lee said, “The isotropic materials that have so far been studied experimentally had limited spectral control over the near-field thermal radiation. Our near-field thermal radiation control technology using multilayer nanostructures is expected to become the first step toward developing various near-field thermal radiation applications.” This research, led by PhD Mikyung Lim and PhD candidate Jaeman Song, was published in Nature Communications on October 16. Figure 1. Experimental setup for measuring near-field thermal radiation between MD multilayers Figure 2. Investigation of manipulated near-field heat flux by modifying the surface conditions with MD multilayers
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