research
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Highly Flexible Organic Flash Memory for Foldable and Disposable Electronics
A KAIST team reported ultra-flexible organic flash memory that is bendable down to a radius of 300μm. The memory exhibits a significantly-long projected retention rate with a programming voltage on par with the present industrial standards.
A joint research team led by Professor Seunghyup Yoo of the School of Electrical Engineering and Professor Sung Gap Im of the Department of Chemical and Biomolecular Engineering said that their memory technology can be applied to non-conventional substrates, such as plastics and papers, to demonstrate its feasibility over a wide range of applications.
With Dr. Seungwon Lee and Dr. Hanul Moon playing the role of leading authors, the research was published in Nature Communications on September 28.
Flash memory is a non-volatile, transistor-based data-storage device that has become essential in most electronic systems in daily life. With straightforward operation mechanisms and easy integration into NAND or NOR array architecture, flash memory has been established as the most successful and dominant non-volatile memory technology by far.
Despite promising demonstrations in the early stages of organic electronics, the overall progress in this field has been far slower than that of thin-film transistors (TFTs) or other devices based on flexible materials. It has been challenging, in particular, to develop flash memory that simultaneously exhibits a significant level of flexibility and performance. This is mainly due to the scarcity of flexible dielectric layers, which are responsible for the tunneling and blocking of charges.
The solution processing used for the preparation of most of the polymeric dielectric layers also makes it difficult to use them in flash memory due to the complexity involved in the formation of the bilayer dielectric structure, which is the key to flash memory operations.
The research team tried to overcome these hurdles and realize highly flexible flash memory by employing thin polymeric insulators grown with initiated chemical vapor deposition (iCVD), a vapor-phase growth technique for polymers that was previously shown to be promising for the fabrication of flexible TFTs. It was further shown that these iCVD-based polymeric insulators, when coupled with rational device design and material choice, can make a significant contribution to flash memory as well.
Memory using conventional polymer insulating films has often required a voltage as high as 100 V (volt) in order to attain long memory retention. If the device is made to operate at a low voltage, the short retention period of less than a month was problematic.
The KAIST team produced flash memory with programming voltages around 10 V and a projected data retention time of over 10 years, while maintaining its memory performance even at a mechanical strain of 2.8%. This is a significant improvement over the existing inorganic insulation layer-based flash memory that allowed only a 1% strain.
The team demonstrated the virtually foldable memory devices by fabricating the proposed flash memory on a 6-micrometer-thick ultrathin plastic film. In addition, it succeeded in producing them on printing paper, opening a way for disposable smart electronic products such as electronic paper and electronic business card.
Professor Yoo said, " This study well illustrates that even highly flexible flash memory can be made to have a practically viable level of performance, so that it contributes to full-fledged wearable electronic devices and smart electronic paper."
(Figure 1. Structure of flexible flash memory )
(Figure 2. Foldable flash memory)
2017.11.06 View 8558 -
Highly Sensitive and Fast Indoor GNSS Signal Acquisition Technology
(Professor Seung-Hyun Kong (right) and Research Fellow Tae-Sun Kim)
A research team led by Professor Seung-Hyun Kong at the Cho Chun Shik Graduate School of Green Transportation, KAIST, developed high-speed, high-sensitivity Global Navigation Satellite System (GNSS) signal acquisition (search and detection) technology that can produce GNSS positioning fixes indoors.
Using the team’s new technology, GNSS signals will be sufficient to identify locations anywhere in the world, both indoors and outdoors. This new research finding was published in the international journal IEEE Signal Processing Magazine (IEEE SPM) this September.
Global Positioning System (GPS) developed by the U.S. Department of Defense in the 1990s is the most widely-used satellite-based navigation system, and GNSS is a terminology to indicate conventional satellite based navigation systems, such as GPS and Russian GLONASS, as well as new satellite-based navigation systems under development, such as European GALILEO, Chinese COMPASS, and other regional satellite-based navigation systems.
In general, GNSS signals are transmitted all over the globe from 20,000 km above the Earth and thus a GNSS signal received by a small antennae in an outdoor environment has weak signal power. In addition, GNSS signals penetrating building walls become extremely weak so the signal can be less than 1/1000th of the signal power received outside.
Using conventional acquisition techniques including the frequency-domain correlation technique to acquire an extremely weak GNSS signal causes the computational cost to increase by over a million times and the processing time for acquisition also increases tremendously. Because of this, indoor measurement techniques using GNSS signals were considered practically impossible for the last 20 years.
To resolve such limitations, the research team developed a Synthesized Doppler-frequency Hypothesis Testing (SDHT) technique to dramatically reduce the acquisition time and computational load for extremely weak GNSS signals indoors.
In general, GNSS signal acquisition is a search process in which the instantaneous accurate code phase and Doppler frequency of the incoming GNSS signal are identified. However, the number of Doppler frequency hypotheses grows proportionally to the coherent correlation time that should be necessarily increased to detect weak signals. In practice, the coherent correlation time should be more than 1000 times longer for extremely weak GNSS signals so the number of Doppler frequency hypotheses is greater than 20,000. On the other hand, the SDHT algorithm indirectly tests the Doppler frequency hypothesis utilizing the coherent correlation results of neighboring hypotheses.
Therefore, using SDHT, only around 20 hypotheses are tested using conventional correlation techniques and the remaining 19,980 hypotheses are calculated with simple mathematical operations. As a result, SDHT achieves a huge computational cost reduction (by about 1000 times) and is 800 times faster for signal acquisition compared to conventional techniques. This means only about 15 seconds is required to detect extremely weak GNSS signals in buildings using a personal computer.
The team predicts further studies for strengthening SDHT technology and developing positioning systems robust enough to multipath in indoor environments will allow indoor GNSS measurements within several seconds inside most buildings using GNSS alone.
Professor Kong said, “This development made us the leader in indoor GNSS positioning technology in the world.” He continued, “We hope to commercialize indoor GNSS systems to create a new market.” The research team is currently registering a patent in Korea and applying for patents overseas, as well as planning to commercialize the technology with the help of the Institute for Startup KAIST.
(Figure1. Positioning Results for the GPS Indoor Positioning System using SDHT Technology)
2017.11.02 View 6373 -
Platinum Single Atom Catalysts for 'Direct Formic Acid Fuel Cells'
(Professor Hyunjoo Lee (left) and Ph.D. candidate Jiwhan Kim)
A research team co-led by Professor Hyunjoo Lee at the Department of Chemical and Biomolecular Engineering at KAIST and Professor Jeong Woo Han from the University of Seoul synthesized highly stable high-Pt-content single atom catalysts for direct formic acid fuel cells. The amount of platinum can be reduced to 1/10 of that of conventional platinum nanoparticle catalysts.
Platinum (Pt) catalysts have been used in various catalytic reactions due to their high activity and stability. However, because Pt is rare and expensive, it is important to reduce the amount of Pt used. Pt single atom catalysts can reduce the size of the Pt particles to the size of an atom. Thus, the cost of Pt catalysts can be minimized because all of the Pt atoms can participate in the catalytic reactions. Additionally, single atom catalysts have no ensemble site in which two or more atoms are attached, and thus, the reaction selectivity is different from that of nanoparticle catalysts.
Despite these advantages, single atom catalysts are easily aggregated and less stable due to their low coordination number and high surface free energy. It is difficult to develop a single atom catalyst with high content and high stability, and thus, its application in practical devices is limited.
Direct formic acid fuel cells can be an energy source for next-generation portable devices because liquid formic acid as a fuel is safer and easier to store and transport than high-pressure hydrogen gas.
To improve the stability of Pt single atom catalysts, Professor Lee’s group developed a Pt-Sn single atom alloy structure on an antimony-doped tin oxide (ATO) support. This structure has been proven by computational calculations which show that Pt single atoms substitute antimony sites in the antimony-tin alloy structure and are thermodynamically stable. This catalyst has been shown to have a higher activity up to 50 times per weight of Pt than that of the commercial catalyst, Pt/C, in the oxidation of formic acid, and the stability of the catalyst was also remarkably high.
Professor Lee’s group also used a single atomic catalyst in a 'direct formic acid fuel cell’ consisting of membranes and electrodes. It is the first attempt to apply a single atomic catalyst to a full cell. In this case, an output similar to that of the commercial catalyst could be obtained by using 1/10 of the platinum compared to the commercial Pt/C catalyst.
Ph.D. candidate Jiwhan Kim from KAIST was the first author of the research. This research was published online on September 11 in Advanced Energy Materials.
This research was carried out with the support of the Samsung Electronics Future Technology Development Center.
(Figure 1. Concept photograph for Pt single atom catalysts.)
(Figure 2. Pt single atom catalysts by HAADF-STEM analysis (bright white circles))
2017.10.31 View 6932 -
High-Speed Motion Core Technology for Magnetic Memory
(Professor Kab-Jin Kim of the Department of Physics)
A joint research team led by Professor Kab-Jin Kim of the Department of Physics, KAIST and Professor Kyung-Jin Lee at Korea University developed technology to dramatically enhance the speed of next generation domain wall-based magnetic memory. This research was published online in Nature Materials on September 25.
Currently-used memory materials, D-RAM and S-RAM, are fast but volatile, leading to memory loss when the power is switched off. Flash memory is non-volatile but slow, while hard disk drives (HDD) have greater storage but are high in energy usage and weak in physical shock tolerance.
To overcome the limitations of existing memory materials, ‘domain wall-based, magnetic memory’ is being researched. The core mechanism of domain wall magnetic memory is the movement of a domain wall by the current. Non-volatility is secured by using magnetic nanowires and the lack of mechanical rotation reduced power usage. This is a new form of high density, low power next-generation memory.
However, previous studies showed the speed limit of domain wall memory to be hundreds m/s at maximum due to the ‘Walker breakdown phenomenon’, which refers to velocity breakdown from the angular precession of a domain wall. Therefore, there was a need to develop core technology to remove the Walker breakdown phenomenon and increase the speed for the commercialization of domain wall memory.
Most domain wall memory studies used ferromagnetic bodies, which cannot overcome the Walker breakdown phenomenon. The team discovered that the use of ‘ferrimagnetic‘ GdFeCo at certain conditions could overcome the Walker breakdown phenomenon and using this mechanism they could increase domain wall speed to over 2Km/s at room temperature.
Domain wall memory is high-density, low-power, and non-volatile memory. The memory could be the leading next-generation memory with the addition of the high speed property discovered in this research.
Professor Kim said, “This research is significant in discovering a new physical phenomenon at the point at which the angular momentum of a ferrimagnetic body is 0 and it is expected to advance the implementation of next-generation memory in the future.”
This research was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (No. 2017R1C1B2009686, NRF-2016R1A5A1008184) and by the DGIST R&D Program of the Ministry of Science, ICT and Future Planning (17-BT-02).
(Figure 1. Concept Map of Domain Wall Memory Material using Ferrimagnetic Body)
(Figure 2. Scheme and Experimental Results of Domain Wall Speed Measurements)
2017.10.30 View 7624 -
Development of a Highly-Accurate Computational Model of Human Metabolism
A research team from KAIST developed a computational framework that enables the reconstruction of a comprehensive computational model of human metabolism, which allows for an accurate prediction of personal metabolic features (or phenotypes).
Understanding personal metabolic phenotypes allows us to design effective therapeutic strategies for various chronic and infectious diseases. A human computational model called the genome-scale metabolic model (GEM) contains information on thousands of metabolic genes and their corresponding reactions and metabolites, and has played an important role in predicting metabolic phenotypes. Although several versions of human GEMs have been released, they had room for further development, especially as to incorporating biological information coming from a human genetics mechanism called “alternative splicing.” Alternative splicing is a genetic mechanism that allows a gene to give rise to multiple reactions, and is strongly associated with pathology.
To tackle this problem, Jae Yong Ryu (a Ph.D. student), Dr. Hyun Uk Kim (Research Fellow), and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at KAIST, developed a computational framework that systematically generates metabolic reactions, and adds them to the human GEM. The resulting human GEM was demonstrated to accurately predict metabolic phenotypes under varied environmental conditions. The research results were published online in Proceedings of the National Academy of Sciences (PNAS) on October 24, 2017, under the title “Framework and resource for more than 11,000 gene-transcript-protein-reaction associations in human metabolism.”
The research team first updated the biological contents of a previous version of the human GEM. The updated biological contents include metabolic genes and their corresponding metabolites and reactions. In particular, metabolic reactions catalyzed by already-known protein isoforms were additionally incorporated into the human GEM; protein isoforms are multiple variants of proteins generated from individual genes through the alternative splicing process. Each protein isoform is often responsible for the operation of a metabolic reaction. Although multiple protein isoforms generated from one gene can play different functions by having different sets of protein domains and/or subcellular localizations, such information was not properly considered in previous versions of human GEMs.
Upon the initial update of the human GEM, named Recon 2M.1, the research team subsequently implemented a computational framework that systematically generates information on Gene-Transcript-Protein-Reaction Associations (GeTPRA) in order to identify protein isoforms that were previously not identified. This framework was developed in this study. As a result of the implementation of the framework for GeTPRA, more than 11,000 GeTPRA were automatically predicted, and thoroughly validated. Additional metabolic reactions were then added to Recon 2M.1 based on the predicted GeTPRA for the previously uncharacterized protein isoforms; Recon 2M.1 was renamed Recon 2M.2 from this upgrade.
Finally, Recon 2M.2 was integrated with 446 sets of personal biological data (RNA-Seq data) in order to build patient-specific cancer models. These patient-specific cancer models were used to predict cancer metabolism activities and anticancer targets.
The development of a new version of human GEMs along with the computational framework for GeTPRA is expected to boost studies in fundamental human genetics and medicine. Model files of the human GEMs Recon 2M.1 and 2M.2, a full list of the GeTPRA and the source code for the computational framework to predict the GeTPRA are all available as part of the publication of this study.
Distinguished Professor Lee said, “The predicted GeTPRA from the computational framework is expected to serve as a guideline for future experiments on human genetics and biochemistry, whereas the resulting Recon 2M.2 can be used to predict drug targets for various human diseases.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea.
(Figure 1:A scheme of Recon 2M.1 development and its use in reconstructing personal genome-scale metabolic models (GEMs). (A) A concept of alternative splicing of human genes and its use in Gene-Transcript-Protein-Reaction Associations (GeTPRA) of Recon 2M.1. (B) A procedure of systematic refinement of the Recon 2Q. Recon 2Q is one of the previously released human GEMs. Biochemically inconsistent reactions include unbalanced, artificial, blocked, and/or redundant reactions. Iterative manual curation was conducted while validating the Recon 2M.1. (C) Reconstruction of cancer patient-specific GEMs using Recon 2M.1 for further simulation studies. In this study, personal biological data (RNA-Seq data) were obtained from The Cancer Genome Atlas (TCGA; https://cancergenome.nih.gov/ ) across the ten cancer types.
(Figure 2: Computational framework for the systematic generation of Gene-Transcript-Protein-Reaction Associations (GeTPRA; red box in the flowchart). Peptide sequences of metabolic genes defined in Recon 2M.1 were retrieved from a database called Ensembl. EC numbers and subcellular localizations of all the protein isoforms of metabolic genes in Recon 2M.1 were predicted using software programs EFICAz2.5 and Wolf PSort, respectively. Information on the newly predicted GeTPRA was systematically incorporated into the Recon 2M.1, thereby resulting in Recon 2M.2.)
2017.10.25 View 8650 -
Ultra-Fast and Ultra-Sensitive Hydrogen Sensor
(From left: Professor Kim, Ph.D. candidate Koo, and Professor Penner)
A KAIST team made an ultra-fast hydrogen sensor that can detect hydrogen gas levels under 1% in less than seven seconds. The sensor also can detect hundreds of parts per million levels of hydrogen gas within 60 seconds at room temperature.
A research group under Professor Il-Doo Kim in the Department of Materials Science and Engineering at KAIST, in collaboration with Professor Reginald M. Penner of the University of California-Irvine, has developed an ultra-fast hydrogen gas detection system based on a palladium (Pd) nanowire array coated with a metal-organic framework (MOF).
Hydrogen has been regarded as an eco-friendly next-generation energy source. However, it is a flammable gas that can explode even with a small spark. For safety, the lower explosion limit for hydrogen gas is 4 vol% so sensors should be able to detect the colorless and odorless hydrogen molecule quickly. The importance of sensors capable of rapidly detecting colorless and odorless hydrogen gas has been emphasized in recent guidelines issued by the U.S. Department of Energy. According to the guidelines, hydrogen sensors should detect 1 vol% of hydrogen in air in less than 60 seconds for adequate response and recovery times.
To overcome the limitations of Pd-based hydrogen sensors, the research team introduced a MOF layer on top of a Pd nanowire array. Lithographically patterned Pd nanowires were simply overcoated with a Zn-based zeolite imidazole framework (ZIF-8) layer composed of Zn ions and organic ligands. ZIF-8 film is easily coated on Pd nanowires by simple dipping (for 2–6 hours) in a methanol solution including Zn (NO3)2·6H2O and 2-methylimidazole.
(This cover image depicts lithographically-patterned Pd nanowires overcoated with a Zn-based zeolite imidazole framework (ZIF-8) layer.)
As synthesized ZIF-8 is a highly porous material composed of a number of micro-pores of 0.34 nm and 1.16 nm, hydrogen gas with a kinetic diameter of 0.289 nm can easily penetrate inside the ZIF-8 membrane, while large molecules (> 0.34 nm) are effectively screened by the MOF filter. Thus, the ZIF-8 filter on the Pd nanowires allows the predominant penetration of hydrogen molecules, leading to the acceleration of Pd-based H2 sensors with a 20-fold faster recovery and response speed compared to pristine Pd nanowires at room temperature.
Professor Kim expects that the ultra-fast hydrogen sensor can be useful for the prevention of explosion accidents caused by the leakage of hydrogen gas. In addition, he expects that other harmful gases in the air can be accurately detected through effective nano-filtration by using of a variety of MOF layers.
This study was carried out by Ph.D. candidate Won-Tae Koo (first author), Professor Kim (co-corresponding author), and Professor Penner (co-corresponding author). The study has been published in the online edition of ACS Nano, as the cover-featured image for the September issue.
Figure 1. Representative image for this paper published in ACS Nano, August, 18.
Figure 2. Images of Pd nanowire array-based hydrogen sensors, scanning electron microscopy image of a Pd nanowire covered by a metal-organic framework layer, and the hydrogen sensing properties of the sensors.
Figure 3. Schematic illustration of a metal-organic framework (MOF). The MOF, consisting of metal ions and organic ligands, is a highly porous material with an ultrahigh surface area. The various structures of MOFs can be synthesized depending on the kinds of metal ions and organic ligands.
2017.09.28 View 9985 -
Photoacoustic Imaging and Photothermal Cancer Therapy Using BR Nanoparticles
(Professor Sangyong Jon and PhD Candidate Dong Yun Lee)
Sangyong Jon, a professor in the Department of Biological Sciences at KAIST, and his team developed combined photoacoustic imaging and photothermal therapy for cancer by using Bilirubin (BR) nanoparticles.
The research team applied the properties of a bile pigment called BR, which exerts potent antioxidant and anti-inflammatory effects, to this research.
The team expects this research, which shows high biocompatibility as well as outstanding photoacoustic imaging and photothermal therapy, to be an appropriate system in the field of treatment for cancer.
In the past, the research team developed a PEGylated bilirubin-based nanoparticle system by combining water-insoluble BR with water-soluble Polyethylene Glycol (PEG).
This technology facilitated BR exerting antioxidants yet prevented them from being accumulated in the body. Its efficiency and safety was identified in an animal disease model, for conditions such as inflammatory bowel disease, islet cell transportation, and asthma.
Differing from previous research methods, this research applied the different physicochemical properties of BR to cancer treatment.
When the causative agent of jaundice, yellow BR, is exposed to a certain wavelength of blue light, the agent becomes a photonic nanomaterial as it responses to the light. This light-responsive nanomaterial can be used to cure jaundice because it allows for active excretion in infants.
Secondly, the team identified that BR is a major component of black pigment gallstones which can be often found in gall bladders or bile ducts under certain pathological conditions. The findings show that BR forms black pigment gallstones without the role of an intermediate or cation, such as calcium and copper. The research team combined cisplatin, a platinum metal-based anticancer drug, with BR so that BR nanoparticles changed the solution color from yellow to purple.
The team also examined the possibility of cisplatin-chelated BR nanoparticles as a probe for photoacoustic images. They found that considerable photoacoustic activity was shown when it was exposed to near infrared light. In fact, the photoacoustic signal was increased significantly in tumors of animals with colorectal cancer when the nanoparticles were administered to it intravenously. The team expects a more accurate diagnosis of tumors through this technology.
Moreover, the team assessed the photothermal effects of cisplatin-chelated BR nanoparticles. The research showed that the temperature of tumors increased by 25 degrees Celsius within five minutes when they were exposed to near infrared light, due to the photothermal effect. After two weeks, their size was reduced compared to that of other groups, and sometimes the tumors were even necrotized.
Professor Jon said, “Existing substances have a low biocompatibility and limitation for clinical therapy because they are artificially oriented; therefore, they might have toxicity. I am hoping that these cisplatin-chelated BR-based nanoparticles will provide a new platform for preclinical, translational research and clinical adaptation of the photoacoustic imaging and photothermal therapy.”
The paper (Dong Yun Lee as a first author) was published online in the renowned journal in the field of applied chemistry, Angewandte Chemi International Edition, on September 4. This research was sponsored by the National Research Foundation of Korea.
(Schematic diagram of the research)
(From left: Bilirubin nanoparticles, cisplatin-chelated Bilirubin nanoparticles)
2017.09.26 View 8068 -
Unlocking the Keys to Parkinson's Disease
A KAIST research team has identified a new mechanism that causes the hallmark symptoms of Parkinson’s disease, namely tremors, rigidity, and loss of voluntary movement.
The discovery, made in collaboration with Nanyang Technological University in Singapore, presents a new perspective to three decades of conventional wisdom in Parkinson’s disease research. It also opens up new avenues that can help alleviate the motor problems suffered by patients of the disease, which reportedly number more than 10 million worldwide. The research was published in Neuron on August 30.
The research team was led by Professor Daesoo Kim from the Department of Biological Sciences at KAIST and Professor George Augustine from the Lee Kong Chian School of Medicine at NTU. Dr. Jeongjin Kim, a former postdoctoral fellow at KAIST who now works at the Korea Institute of Science and Technology (KIST), is the lead author.
It is known that Parkinson’s disease is caused by a lack of dopamine, a chemical in the brain that transmits neural signals. However, it remains unknown how the disease causes the motor
Smooth, voluntary movements, such as reaching for a cup of coffee, are controlled by the basal ganglia, which issue instructions via neurons (nerve cells that process and transmit information in the brain) in the thalamus to the cortex. These instructions come in two types: one that triggers a response (excitatory signals) and the other that suppresses a response (inhibitory signals). Proper balance between the two controls movement.
A low level of dopamine causes the basal ganglia to severely inhibit target neurons in the thalamus, called an inhibition. Scientists have long assumed that this stronger inhibition causes the motor problems of Parkinson’s disease patients.
To test this assumption, the research team used optogenetic technology in an animal model to study the effects of this increased inhibition of the thalamus and ultimately movement. Optogenetics is the use of light to control the activity of specific types of neurons within the brain.
They found that when signals from the basal ganglia are more strongly activated by light, the target neurons in the thalamus paradoxically became hyperactive. Called rebound excitation, this hyperactivity produced abnormal muscular stiffness and tremor. Such motor problems are very similar to the symptoms of Parkinson’s disease patients. When this hyperactivity of thalamic neurons is suppressed by light, mice show normal movments without Parkinson’s disease symptoms. Reducing the levels of activity back to normal caused the motor symptoms to stop, proving that the hyperactivity caused the motor problems experienced by Parkinson’s disease patients.
Professor Kim at KAIST said, “This study overturns three decades of consensus on the provenance of Parkinsonian symptoms.” The lead author, Dr Jeongjin Kim said, “The therapeutic implications of this study for the treatment of Parkinsonian symptoms are profound. It may soon become possible to remedy movement disorders without using L-DOPA, a pre-cursor to dopamine.”
Professor Augustine at NTU added, “Our findings are a breakthrough, both for understanding how the brain normally controls the movement of our body and how this control goes awry during Parkinson’s disease and related dopamine-deficiency disorders.”
The study took five years to complete, and includes researchers from the Department of Bio & Brain Engineering at KAIST.
The research team will move forward by investigating how hyperactivity in neurons in the thalamus leads to abnormal movement, as well as developing therapeutic strategies for the disease by targeting this neural mechanism.
Figure abstract: Inhibitory inputs from the basal ganglia inhibit thalamic neurons (upper). In low-dopamine states, like PD, rebound firing follows inhibition and causes movement disorders (middle). The inhibition of rebound firing alleviates PD-like symptoms in a mouse model of PD.
2017.09.22 View 9479 -
Draining Eyes Clogged with Glaucoma
Professor Gou Young Koh in the Graduate School of Medical Science and Engineering and his team have identified a new mechanism involved in the development and progression of glaucoma, and found a potential therapeutic option to treat it. Glaucoma is the second cause of irreversible blindness, after cataracts. It affects about 3.5% of the world population aged 40 to 80.
Professor Koh also serves as the director of the Center for Vascular Research at the Institute for Basic Science. The IBS said the study, published in the Journal of Clinical Investigation, is expected to help the development of therapies to treat primary open-angle glaucoma (POAG), which counts for three quarters of all glaucoma patients.
One of the most important risk factors for glaucoma is the increased pressure inside the eye. A liquid called aqueous humor is constantly produced and drained out from the eye. It transports nutrients and inflates the eye giving it a roughly spherical shape. However, if this fluid cannot flow out of the eye chambers freely, an increase in intraocular pressure can damage the optic nerve, leading to vision loss. The precise mechanism of elevated resistance to aqueous humor outflow remains unclear, and although the current treatments for glaucoma tackle the production and outflow of aqueous humor, their outcomes are still poor.
A component of the eye that plays a fundamental role in draining out the aqueous humor is Schlemm's canal. It collects the aqueous humor and mediates its transfer from the eye chambers to blood circulation. The cells on the walls of the canal, endothelial cells, ship the liquid from the inner to the outer side in “packages”, called vacuoles. As the shape and number of the vacuoles reflects the outflow performance, several giant vacuoles are expected in the normal outflow process.
The team explained how imbalances in Schlemm's canal significantly increase the risk of glaucoma. They showed that an important regulator for canal functionality is the angiopoietin-Tie2 system. Angiopoietins, such as Ang1 and Ang2, are proteins important for the growth of new blood vessels and Tie2 is the receptor that binds them. It is known that the angiopoietin-Tie2 system plays a role in Schlemm’s canal formation, as Tie2 mutations or angiopoietin absence result in congenital glaucoma. However, this study clarified that it is also critically important during adulthood.
The researchers reported that adult mice deficient in Tie2 suffer from an elevated intraocular pressure, retinal neuronal damage and partial visual impairment. Moreover, they had a markedly decreased number of giant vacuoles inside Schlemm’s canal endothelial cells, which indicate a poor aqueous humor drainage.
The scientists also investigated if and how this process changes in older mice, as aging is a major risk factor for glaucoma, and showed that aged mice experience reduced levels of giant vacuoles, Tie2, Ang1, and Ang2, as well as other proteins connected with the angiopoietin-Tie2 pathway, like Prox1.
To test whether Tie2 activation could shift the situation, the researchers tested the antibody ABTAA (Ang2-binding and Tie2-activating antibody). They injected it in one eye of mice, while the other eye of the same mice functioned as the negative control. After one week, levels of Tie2 and Prox1, number and diameter of giant vacuoles in Schlemm’s canals increased in the ABTAA-treated eyes compared to control eyes. The researchers observed a similar outcome with decreased intraocular pressure when ABTAA was injected to the eyes of mice suffering from POAG with regressed Schlemm’s canals, indicating that this antibody might be considered as a therapeutic option.
"Slow development of glaucoma treatments is partly due to the poor understanding of the underlying pathogenesis," said Professor Koh, the corresponding author of the study. "We hope that identifying the critical role of the angiopoietin-Tie2 system in adult Schlemm’s canals will bring a significant boost in the development of therapeutics."
Figure 1: Schlemm's canal position inside the eye.
Schlemm's canal (green) plays a fundamental role in draining the aqueous humor (white arrows) from the anterior chamber of the eye to blood circulation. If the aqueous humor is not able to flow out freely, elevated intraocular pressure damages the optical nerve causing glaucoma and eventually blindness.
Figure 2: Electron microscope images reveal how the aqueous humor is packaged in vacuoles (arrowheads) inside the cells forming the walls of Schlemm's canal.
Aging and glaucoma cause the number and size of giant vacuoles to decrease, meaning that the aqueous humor outflow is compromised. The images compare the giant vacuoles in Schlemm's canals of a healthy mouse (top) and a mouse lacking Tie2 (bottom)
Figure 3: The Ang2-binding and Tie2-activating antibody (ABTAA) rejuvenates the eye of aged mice and rescues them from glaucoma.
Aging causes a reduction of the protein Tie2, a risk factor for increased intraocular pressure and glaucoma. In this experiment, one eye of mice lacking Ang1 and Ang2 was injected with the premixed ABTAA and Ang2, while the other eye was used as negative control. The researchers observed an increase in the area of Schlemm’s canal, together with higher levels of Tie2 (red) and lower intraocular pressure, suggesting that ABTAA restores the canal's functionality. The image includes the transcription factor Prox1 (green) and CD144 (blue), a protein present at the junctions between cells that form the wall of the canal. The angiopoietin-Tie2 system and Prox1 are linked by a vicious circle: the less Tie2 and Ang2, the less Prox1, leading to Schlemm's canal damage, increase in intraocular pressure, and acceleration of glaucoma progression.
2017.09.19 View 6664 -
Semiconductor Patterning of Seven Nanometers Technology Using a Camera Flash
A research team led by Professor Sang Ouk Kim in the Department of Materials Science and Engineering at KAIST has developed semiconductor manufacturing technology using a camera flash.
This technology can manufacture ultra-fine patterns over a large area by irradiating a single flash with a seven-nanometer patterning technique for semiconductors. It can facilitate the manufacturing of highly efficient, integrated semiconductor devices in the future.
Technology for the Artificial Intelligence (AI), the Internet of Things (IoTs), and big data, which are the major keys for the fourth Industrial Revolution, require high-capacity, high-performance semiconductor devices. It is necessary to develop lithography technology to produce such next-generation, highly integrated semiconductor devices.
Although related industries have been using conventional photolithography for small patterns, this technique has limitations for forming a pattern of sub-10 nm patterns.
Molecular assembly patterning technology using polymers has been in the spotlight as the next generation technology to replace photolithography because it is inexpensive to produce and can easily form sub-10 nm patterns. However, since it generally takes a long time for heat treatment at high-temperature or toxic solvent vapor treatment, mass production is difficult and thus its commercialization has been limited.
The research team introduced a camera flash that instantly emits strong light to solve the issues of polymer molecular assembly patterning. Using a flash can possibly achieve a semiconductor patterning of seven nanometers within 15 milliseconds (1 millisecond = 1/1,000 second), which can generate a temperature of several hundred degrees Celsius in several tens of milliseconds.
The team has demonstrated that applying this technology to polymer molecular assembly allows a single flash of light to form molecular assembly patterns.
The team also identified its compatibility with polymer flexible substrates, which are impossible to process at high temperatures. Through these findings, the technology can be applied to the fabrication of next-generation, flexible semiconductors.
The researchers said the camera flash photo-thermal process will be introduced into molecular assembly technology and this highly-efficiency technology can accelerate the realization of molecular assembly semiconductor technology.
Professor Kim, who led the research, said, “Despite its potential, molecular assembly semiconductor technology has remained a big challenge in improving process efficiency.” “This technology will be a breakthrough for the practical use of molecular assembly-based semiconductors.”
The paper was published in the international journal, Advanced Materials on August 21 with first authors, researcher Hyeong Min Jin and PhD candidate Dae Yong Park.
The research, sponsored by the Ministry of Science and ICT, was co-led Professor by Keon Jae Lee in the Department of Materials Science and Engineering at KAIST, and Professor Kwang Ho Kim in the School of Materials Science and Engineering at Pusan National University.
(1. Formation of semiconductor patterns using a camera flash)
(Schematic diagram of molecular assembly pattern using a camera flash)
(Self-assembled patterns)
2017.09.18 View 10110 -
A Novel and Practical Fab-route for Superomniphobic Liquid-free Surfaces
(clockwise from left: Jaeho Choi, Hee Tak Kim, Shin-Hyun Kim)
A joint research team led by Professor Hee Tak Kim and Shin-Hyun Kim in the Department of Chemical and Biomolecular Engineering at KAIST developed a fabrication technology that can inexpensively produce surfaces capable of repelling liquids, including water and oil.
The team used the photofluidization of azobenzene molecule-containing polymers to generate a superomniphobic surface which can be applied for developing stain-free fabrics, non-biofouling medical tubing, and corrosion-free surfaces.
Mushroom-shaped surface textures, also called doubly re-entrant structures, are known to be the most effective surface structure that enhances resistance against liquid invasion, thereby exhibiting superior superomniphobic property.
However, the existing procedures for their fabrication are highly delicate, time-consuming, and costly. Moreover, the materials required for the fabrication are restricted to an inflexible and expensive silicon wafer, which limits the practical use of the surface.
To overcome such limitations, the research team used a different approach to fabricate the re-entrant structures called localized photofludization by using the peculiar optical phenomenon of azobenzene molecule-containing polymers (referred to as azopolymers). It is a phenomenon where an azopolymer becomes fluidized under irradiation, and the fluidization takes place locally within the thin surface layer of the azopolymer.
With this novel approach, the team facilitated the localized photofluidization in the top surface layer of azopolymer cylindrical posts, successfully reconfiguring the cylindrical posts to doubly re-entrant geometry while the fluidized thin top surface of an azopolymer is flowing down.
The structure developed by the team exhibits a superior superomniphobic property even for liquids infiltrating the surface immediately.
Moreover, the superomniphobic property can be maintained on a curved target surface because its surficial materials are based on high molecules.
Furthermore, the fabrication procedure of the structure is highly reproducible and scalable, providing a practical route to creating robust omniphobic surfaces.
Professor Hee Tak Kim said, “Not only does the novel photo-fluidization technology in this study produce superior superomniphobic surfaces, but it also possesses many practical advantages in terms of fab-procedures and material flexibility; therefore, it could greatly contribute to real uses in diverse applications.”
Professor Shin-Hyun Kim added, “The designed doubly re-entrant geometry in this study was inspired by the skin structure of springtails, insects dwelling in soil that breathe through their skin. As I carried out this research, I once again realized that humans can learn from nature to create new engineering designs.”
The paper (Jaeho Choi as a first author) was published in ACS Nano, an international journal for Nano-technology, in August.
(Schematic diagram of mushroom-shaped structure fabrication)
(SEM image of mushroom-shaped structure)
(Image of superomniphobic property of different types of liquid)
2017.09.08 View 7051 -
Discovery of an Optimal Drug Combination: Overcoming Resistance to Targeted Drugs for Liver Cancer
A KAIST research team presented a novel method for improving medication treatment for liver cancer using Systems Biology, combining research from information technology and the life sciences. Professor Kwang-Hyun Cho in the Department of Bio and Brain Engineering at KAIST conducted the research in collaboration with Professor Jung-Hwan Yoon in the Department of Internal Medicine at Seoul National University Hospital. This research was published in Hepatology in September 2017 (available online from August 24, 2017).
Liver cancer is the fifth and seventh most common cancer found in men and women throughout the world, which places it second in the cause of cancer deaths. In particular, Korea has 28.4 deaths from liver cancer per 100,000 persons, the highest death rate among OECD countries and twice that of Japan.
Each year in Korea, 16,000 people get liver cancer on average, yet the five-year survival rate stands below 12%. According to the National Cancer Information Center, lung cancer (17,399) took the highest portion of cancer-related deaths, followed by liver cancer (11,311) based on last year data.
Liver cancer is known to carry the highest social cost in comparison to other cancers and it causes the highest fatality in earlier age groups (40s-50s). In that sense, it is necessary to develop a new treatment that mitigates side effects yet elevates the survival rate.
There are ways in which liver cancer can be cured, such as surgery, embolization, and medication treatments; however, the options become limited for curing progressive cancer, a stage in which surgical methods cannot be executed.
Among anticancer medications, Sorafenib, a drug known for enhancing the survival rate of cancer patients, is a unique drug allowed for use as a targeted anticancer medication for progressive liver cancer patients. Its sales reached more than ten billion KRW annually in Korea, but its efficacy works on only about 20% of the treated patients. Also, acquired resistance to Sorafenib is emerging. Additionally, the action mechanism and resistance mechanism of Sorafenib is only vaguely identified.Although Sorafenib only extends the survival rate of terminal cancer patients less than three months on average, it is widely being used because drugs developed by global pharmaceutical companies failed to outperform its effectiveness.
Professor Cho’s research team analyzed the expression changes of genes in cell lines in response to Sorafenib in order to identify the effect and the resistance mechanism of Sorafenib.
As a result, the team discovered the resistance mechanism of Sorafenib using Systems Biology analysis. By combining computer simulations and biological experiments, it was revealed that protein disulfide isomerase (PDI) plays a crucial role in the resistance mechanism of Sorafenib and that its efficacy can be improved significantly by blocking PDI.
The research team used mice in the experiment and discovered the synergic effect of PDI inhibition with Sorafenib for reducing liver cancer cells, known as hepatocellular carcinoma. Also, more PDIs are shown in tissue from patients who possess a resistance to Sorafenib. From these findings, the team could identify the possibility of its clinical applications. The team also confirmed these findings from clinical data through a retrospective cohort study.
“Molecules that play an important role in cell lines are mostly put under complex regulation. For this reason, the existing biological research has a fundamental limitations for discovering its underlying principles,” Professor Cho said. “This research is a representative case of overcoming this limitation of traditional life science research by using a Systems Biology approach, combining IT and life science. It suggests the possibility of developing a new method that overcomes drug resistance with a network analysis of the targeted drug action mechanism of cancer.”
The research was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT.
(Figure 1. Simulation results from cellular experiments using hepatocellular carcinoma)
(Figure 2. Network analysis and computer simulation by using the endoplasmic reticulum (ER) stress network)
(Figure 3. ER stress network model)
2017.08.30 View 10446