research
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Analysis of Gas Adsorption Properties for Amorphous Porous Materials
Professor Jihan Kim from the Department of Chemical and Biomolecular Engineering at KAIST has developed a method to predict gas adsorption properties of amorphous porous materials.
Metal-organic frameworks (MOFs) have large surface area and high density of pores, making them appropriate for various energy and environmental-related applications. And although most MOFs are crystalline, these structures can deform during synthesis and/or industrial processes, leading to loss in long-range order. Unfortunately, without the structural information, existing computer simulation techniques cannot be used to model these materials.
In this research, Professor Kim’s research team demonstrated that one can replace the material properties of structurally deformed MOFs with those of crystalline MOFs to indirectly analyze/model the material properties of amorphous materials. First, the team conducted simulations on methane gas adsorption properties for over 12,000 crystalline MOFs to obtain a large training set data, and created a resulting structure-property map. Upon mapping the experimental data of amorphous MOFs onto the structure-property map, results showed that regardless of crystallinity, the gas adsorption properties of MOFs showed congruence and consistency amongst one another.
Based on these findings, selected crystalline MOFs with the most similar gas adsorption properties as the collapsed structure from the 12,000 candidates. Then, the team verified that the adsorption properties of these similar MOFs can be successfully transferred to the deformed MOFs across different temperatures and even to different gas molecules (e.g. hydrogen), demonstrating transferability of properties.
These findings allow material property prediction in porous materials such as MOFs without structural information, and the techniques here can be used to better predict and understand optimal materials for various applications including, carbon dioxide capture, gas storage and separations.
This research was conducted in collaboration with Professor Dae-Woon Lim at Kyoto University, Professor Myunghyun Paik at Seoul National University, Professor Minyoung Yoon at Gachon University, and Aadesh Harale at Saudi Arabian Oil Company. The research was published in the Proceedings of the National Academy of Sciences (PNAS) online on 10 July and the co-first authors were Ph. D. candidate WooSeok Jeong and Professor Dae-Woon Lim.
This research was funded by the Saudi Aramco-KAIST CO2 Management Center.
(Figure 1. Trends in structure - material property map and in collapsed structures)
(Figure 2. Transferability between the experimental results of collapsed MOFs and the simulation results of crystalline MOFs)
2017.07.26 View 9786 -
Innovative Nanosensor for Disease Diagnosis
(Figure 1. Sensing Device)
(Figure 2. Protein templating route)
Breath pattern recognition is a futuristic diagnostic platform. Simple characterizing target gas concentrations of human exhaled breath will lead to diagnose of the disease as well as physical condition.
A research group under Prof. Il-Doo Kim in the Department of Materials Science has developed diagnostic sensors using protein-encapsulated nanocatalysts, which can diagnose certain diseases by analyzing human exhaled breath. This technology enables early monitoring of various diseases through pattern recognition of biomarker gases related to diseases in human exhalation.
The protein-templated catalyst synthesis route is very simple and versatile for producing not only a single component of catalytic nanoparticles, but also diverse heterogeneous intermetallic catalysts with sizes less than 3 nm. The research team has developed ever more sensitive and selective chemiresistive sensors that can potentially diagnose specific diseases by analyzing exhaled breath gases.
The results of this study, which were contributed by Dr. Sang-Joon Kim and Dr. Seon-Jin Choi as first authors were selected as the cover-featured article in the July issue of 'Accounts of Chemical Research,' an international journal of the American Chemical Society.
In human breath, diverse components are found including water vapor, hydrogen, acetone, toluene, ammonia, hydrogen sulfide, and carbon monoxide, which are more excessively exhaled from patients. Some of these components are closely related to diseases such as asthma, lung cancer, type 1 diabetes mellitus, and halitosis.
Breath analysis for disease diagnosis started from capturing exhaled breaths in a Tedlar bag and subsequently the captured breath gases were injected into a miniaturized sensor system, similar to an alcohol detector. It is possible to analyze exhaled breath very rapidly with a simple analyzing process. The breath analysis can detect trace changes in exhaled breath components, which contribute to early diagnosis of diseases.
However, technological advances are needed to accurately analyze gases in the breath, which occur at very low levels, from 1 ppb to 1 ppm. In particular, it has been a critical challenge for chemiresistive type chemical sensors to selectively detect specific biomarkers in thousands of interfering gases including humid vapor.
Conventionally, noble metallic catalysts such as platinum and palladium have been functionalized onto metal oxide sensing layers. However, the gas sensitivity was not enough to detect ppb-levels of biomarker species in exhaled breath.
To overcome the current limitations, the research team utilized nanoscale protein (apoferritin) in animals as sacrificial templates. The protein templates possess hollow nanocages at the core site and various alloy catalytic nanoparticles can be encapsulated inside the protein nanocages.
The protein nanocages are advantageous because a nearly unlimited number of material compositions in the periodic table can be assembled for the synthesis of heterogeneous catalytic nanoparticles. In addition, intermetallic nanocatalysts with a controlled atomic ratio of two different elements can be achieved using the protein nanocages, which is an innovative strategy for finding new types of catalysts. For example, highly efficient platinum-based catalysts can be synthesized, such as platinum-palladium (PtPd), platinum-nickel (PtNi), platinum-ruthenium (PtRu), and platinum-yttrium (PtY).
The research team developed outstanding sensing layers consisting of metal oxide nanofibers functionalized by the heterogeneous catalysts with large and highly-porous surface areas, which are especially optimized for selective detection of specific biomarkers. The biomarker sensing performance was improved approximately 3~4-fold as compared to the conventional single component of platinum and palladium catalysts-loaded nanofiber sensors. In particular, 100-fold resistance transitions toward acetone (1 ppm) and hydrogen sulfide (1 ppm) were observed in exhaled breath sensors using the heterogeneous nanocatalysts, which is the best performance ever reported in literature.
The research team developed a disease diagnosis platform that recognizes individual breathing patterns by using a multiple sensor array system with diverse sensing layers and heterogeneous catalysts, so that the people can easily identify health abnormalities. Using a 16-sensor array system, physical conditions can be continuously monitored by analyzing concentration changes of biomarkers in exhaled breath gases.
Prof. Kim said, “New types of heterogeneous nanocatalysts were synthesized using protein templates with sizes around 2 nm and functionalized on various metal oxide nanofiber sensing layers. The established sensing libraries can detect biomarker species with high sensitivity and selectivity.” He added, “the new and innovative breath gas analysis platform will be very helpful for reducing medical expenditures and continuous monitoring of physical conditions”
Patents related to this technology were licensed to two companies in March and June this year.
2017.07.19 View 10880 -
Structural Insights into the Modulation of Synaptic Adhesion by MDGA for Synaptogenesis
Synapses connected by various synaptic adhesion molecules are communication spaces between neurons for transmitting information. Among various synaptic adhesion molecules, neuroligins are arguably the most widely studied class of postsynaptic adhesion molecules, which mainly interact with presynaptic neurexins to induce excitatory or inhibitory synapse development. Recently, the membrane-associated mucin (MAM) domain-containing GPI anchor protein 1 (MDGA1) has been characterized as a key suppressor of Neuroligin-2/Neurexin-1β-mediated inhibitory synapse development, but how it acts remains a mystery.
In a recent issue of Neuron, published on June 21, 2017, a research team led by Professor Ho Min Kim at the Graduate School of Medical Science and Engineering of KAIST reported the three-dimensional structure of MDGA1/Neuroligin-2 complex and mechanistic insights into how MDGAs negatively modulate synapse development governed by Neurexins/Neuroligins trans -synaptic adhesion complex.
MDGA1 consists of six Ig-like domains, fibronectin type III repeat domain, and MAM domain . The crystal structure of MDGA1/Neuroligin-2 complex reveals that they form the 2:2 hetero-tetrameric complex and only the Ig1-Ig2 domains of MDGA1 are involved in interactions with Neuroligin-2. The structural comparison between the MDGA1/Neuroligin-2 and Neurexin-1β/Neuroligin-1 complexes intriguingly indicates that the Neuroligin-2 region binding to MDGA1 largely overlaps with that of Neurexin-1β, but the interaction interface of the MDGA1/Neuroligin-2 complex is much larger than that of the Neurexin-1β/Neuroligin-1 complex. This explains why Neuroligin-2 binds stronger to MDGA1 than Neurexin-1β, and how the favored MDGA1 binding to Neuroligin-2 sterically blocks the interaction between Neuroligin-2 and Neurexin-1β, which is critical for the suppression of inhibitory synapse development.
“Although we found that MDGA Ig domains (Ig 1 and Ig 2) are sufficient to form a complex with NL2, other extracellular domains, including Ig 3–6, FN III, and MAM domains, may also contribute to stable cis-interactions between MDGA1 and Neuroligin-2 by providing conformational flexibility. Therefore, further structural analysis of full-length MDGA will be required,” Professor Kim said.
Neuroligin-2 specifically promotes the development of inhibitory synapses, whereas neuroligin-1 promotes the development of excitatory synapses. Recently, not only MDGA1, but also MDGA2 have emerged as synaptic regulators for the development of excitatory or inhibitory synapses. In vitro biochemical analysis in this research clearly demonstrates that Neuroligin-1 and Neuroligin-2 bind to both MDGA1 and MDGA2 with comparable affinity. However, pull-down assays using detergent-solubilized mouse brain membrane fractions show the specific interaction of MDGA1 with Neuroligin-2, but not with Neuroligin-1. “This suggests that unidentified processes may dictate the selective association of MDGA1 with Neuroligin-2 in vivo , ” explained Professor Jaewon Ko at the Daegu Gyeongbuk Institute of Science and Technology (DGIST).
A balance between excitatory and inhibitory synapses is crucial to healthy cognition and behavior. Mutations in neuroligins, neurexins, and MDGAs, which can disrupt the excitatory/inhibitory balance, are associated with neuropsychiatric diseases such as autism and schizophrenia. Jung A Kim at KAIST, first author in this study, said, “Our discovery from integrative investigations are an important first step both for a better understanding of Neuroligin/Neurexin synaptic adhesion pathways and MDGA-mediated regulation of synapse development as well as the development of potential new therapies for autism, schizophrenia, and epilepsy.”
2017.07.10 View 9091 -
Cooperative Tumor Cell Membrane-Targeted Phototherapy
A KAIST research team led by Professor Ji-Ho Park in the Bio and Brain Engineering Department at KAIST developed a technology for the effective treatment of cancer by delivering synthetic receptors throughout tumor tissue. The study, led by Ph.D. candidate Heegon Kim, was published online in Nature Communications on June 19.
Cancer targeted therapy generally refers to therapy targeting specific molecules that are involved in the growth and generation of cancer. The targeted delivery of therapeutics using targeting agents such as antibodies or nanomaterials has improved the precision and safety of cancer therapy.
However, the paucity and heterogeneity of identified molecular targets within tumors have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes.
To solve this problem, the team constructed a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumor cell membrane-selective localization of synthetic receptors to amplify the subsequent targeting of therapeutics. Here, synthetic and biological nanocomponents refer to liposomes and extracellular vesicles, respectively.
The synthetic receptors are first delivered selectively to tumor cell membranes in the perivascular region using liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the synthetic receptors are transferred to neighboring cells and further spread throughout the tumor tissues where the molecular targets are limited.
Hitchhiking extracellular vesicles for delivery of synthetic receptors was possible since extracellular vesicles, such as exosomes, mediate intercellular communications by transferring various biological components such as lipids, cytosolic proteins, and RNA through a membrane fusion process. They also play a supportive role in promoting tumor progression in that tumor-derived extracellular vesicles deliver oncogenic signals to normal host cells.
The team showed that this tumor cell membrane-targeted delivery of synthetic receptors led to a uniform distribution of synthetic receptors throughout a tumor and subsequently led to enhanced phototherapeutic efficacy of the targeted photosensitizer.
Professor Park said, “The cooperative tumor targeting system is expected to be applied in treating various diseases that are hard to target.”
The research was funded by the Basic Science Research Program through the National Research Foundation funded by the Ministry of Science, ICT & Future Planning, and the National R&D Program for Cancer Control funded by the Ministry for Health and Welfare.
(Ph.D. candidates Hee Gon Kim (left) and Chanhee Oh)
Figure 1. A schematic of a cooperative tumor targeting system via delivery of synthetic receptors.
Figure 2. A confocal microscopic image of a tumor section after cooperative targeting by synthetic receptor delivery. Green and magenta represent vessels and therapeutic agents inside a tumor respectively.
2017.07.07 View 11110 -
Top 10 Emerging Technologies of 2017
The World Economic Forum’s Expert Network and Global Future Councils in collaboration with Scientific American and its Board of Advisors announced the top 10 emerging technologies of 2017 on June 26 in Dalian, China where the 2017 Summer Davos Forum is being held. Each technology was chosen for its potential to improve lives, transform industries, and safeguard the planet.
The KAIST delegation, headed by President Sung-Chul Shin, is participating in the forum’s diverse activities including IdeasLab and GULF (Global University Leaders Forum). KAIST is the only Korean representative participating in the IdeasLab. KAIST Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, director of KAIST Institute, has served as a committee member of the Global Agenda Council on Emerging Technologies since 2012 and Global Future Council on the Fourth Industrial Revolution. He also chairs the Global Future Council on Biotechnologies.
Professor Lee said, “Very diverse technological breakthroughs were proposed for the final list of candidates. We made the final selections through very in-depth discussion with experts in each field.
We focused on the technologies which have a level of maturity that will enable them to be adopted widely within three to five years."
The top 10 emerging technologies are
(courtesy from https://
www.weforum.org/agenda/2017/06/these-are-the-top-10-emerging-technologies-of-2017):
2017 10대 기술.
1. Liquid biopsies
Liquid biopsies mark a step forward in the fight against cancer. First, they are an alternative where traditional tissue-based biopsies are not possible. Second, they provide a full spectrum of information compared to tissue samples, which only reflect the information available in the sample. Lastly, by homing in on circulating-tumor DNA (ctDNA), genetic material that routinely finds its way from cancer cells into the bloodstream, disease progression or resistance to treatment can be spotted much faster than otherwise relying on symptoms or imaging.
2. Harvesting clean water from air
The ability to extract clean water from air is not new, however existing techniques require high moisture levels and a lot of electricity. This is changing. A team from MIT and University of California, Berkeley has successfully tested a process using porous crystals that convert the water using no energy at all.
3. Deep learning for visual tasks
Computers are beginning to recognize images better than humans. Thanks to deep learning, an emerging field of artificial intelligence, computer-vision technologies are increasingly being used in applications as diverse as driving autonomous vehicles, medical diagnostics, damage assessment for insurance claims, and monitoring water levels and crop yield.
4. Liquid fuels from sunshine
Can we mimic the humble leaf to create artificial photosynthesis to generate and store energy? The prospects are looking increasingly positive. The answer lies in using sunlight-activated catalysts to split water molecules into water and hydrogen, and then using the same hydrogen to convert CO2 into hydrocarbons.
5. The Human Cell Atlas
An international collaboration aimed at deciphering the human body, called the Human Cell Atlas, was launched in October 2016. The project aims to identify every cell type in every tissue; learn exactly which genes, proteins, and other molecules are active in each type, and the processes which control that activity.
6. Precision farming
The Fourth Industrial Revolution is providing farmers with a new set of tools to boost crop yield and quality while reducing water and chemical use. Sensors, robots, GPS, mapping tools, and data-analytics software are all being used to customize the care that plants need.
7. Affordable catalysts for green vehicles
Progress is being made on a promising zero-emission technology, the hydrogen-fed fuel cell. Progress to date has been stymied by the high price of catalysts which contain platinum. However, much progress has been made in reducing reliance on this rare and expensive metal, and the latest developments involve catalysts that include no platinum, or in some cases no metal at all.
8. Genomic vaccines
Vaccines based on genes are superior to more conventional ones in a number of ways. They are faster to manufacture, which is crucial during violent outbreaks. Compared to manufacturing proteins in cell cultures or eggs, producing genetic material should also be simpler and less expensive.
9. Sustainable design of communities
Applying green construction to multiple buildings at once has the potential to revolutionize the amount of energy and water we consume. Sending locally-generated solar power to a smart microgrid could reduce electricity consumption by half and reduce carbon emissions to zero if a project currently under development at the University of California at Berkeley goes according to plan.
10. Quantum computing
Quantum computers’ almost limitless potential has only ever been matched by the difficulty and cost of their construction. This explains why today the small ones that have been built have not yet managed to exceed the power of supercomputers. But progress is being made and in 2016 the technology firm IBM provided public access to the first quantum computer in the cloud.
2017.06.28 View 13097 -
Why Don't My Document Photos Rotate Correctly?
John, an insurance planner, took several photos of a competitors’ new brochures. At a meeting, he opened a photo gallery to discuss the documents with his colleagues. He found, however, that the photos of the document had the wrong orientation; they had been rotated in 90 degrees clockwise. He then rotated his phone 90 degrees counterclockwise, but the document photos also rotated at the same time. After trying this several times, he realized that it was impossible to display the document photos correctly on his phone. Instead, he had to set his phone down on a table and move his chair to show the photos in the correct orientation. It was very frustrating for John and his colleagues, because the document photos had different patterns of orientation errors.
Professor Uichin Lee and his team at KAIST have identified the key reasons for such orientation errors and proposed novel techniques to solve this problem efficiently. Interestingly, it was due to a software glitch in screen rotation–tracking algorithms, and all smartphones on the market suffer from this error.
When taking a photo of a document, your smartphone generally becomes parallel to the flat surface, as shown in the figure above (right). Professor Lee said, “Your phone fails to track the orientation if you make any rotation changes at that moment.” This is because software engineers designed the rotation tracking software in conventional smartphones with the following assumption: people hold their phones vertically either in portrait or landscape orientations. Orientation tracking can be done by simply measuring the gravity direction using an acceleration sensor in the phone (for example, whether gravity falls into the portrait or landscape direction).
Professor Lee’s team conducted a controlled experiment to discover how often orientation errors happen in document-capturing tasks. Surprisingly, their results showed that landscape document photos had error rates of 93%. Smartphones’ camera apps display the current orientation using a camera-shaped icon, but users are unaware of this feature, nor do they notice its state when they take document photos. This is why we often encounter rotation errors in our daily lives, with no idea of why the errors are occurring.
The team developed a technique that can correct a phone’s orientation by tracking the rotation sensor in a phone. When people take document photos their smartphones become parallel to the documents on a flat surface. This intention of photographing documents can be easily recognizable because gravity falls onto the phone’s surface. The current orientation can be tracked by monitoring the occurrence of significant rotation.
In addition, the research team discovered that when taking a document photo, the user tends to tilt the phone, just slightly, towards the user (called a “micro-tilt phenomenon”). While the tilting degree is very small—almost indistinguishable to the naked eye—these distinct behavioral cues are enough to train machine-learning models that can easily learn the patterns of gravity distributions across the phone.
The team’s experimental results showed that their algorithms can accurately track phone orientation in document-capturing tasks at 93% accuracy. Their approaches can be readily integrated into both Google Android and Apple iPhones. The key benefits of their proposals are that the correction software works only when the intent of photographing documents is detected, and that it can seamlessly work with existing orientation tracking methods without conflict. The research team even suggested a novel user interface for photographing documents. Just like with photocopiers, the capture interface overlays a document shape onto a viewfinder so that the user can easily double-check possible orientation errors.
Professor Lee said, “Photographing documents is part of our daily activities, but orientation errors are so prevalent that many users have difficulties in viewing their documents on their phones without even knowing why such errors happen.” He added, “We can easily detect users’ intentions to photograph a document and automatically correct orientation changes. Our techniques not only eliminate any inconvenience with orientation errors, but also enable a range of novel applications specifically designed for document capturing.” This work, supported by the Korean Government (MSIP), was published online in the International Journal of Human-Computer Studies in March 2017. In addition, their US patent application was granted in March 2017.
(Photo caption: The team of Professor Lee and his Ph.D.student Jeungmin Oh developed a technique that can correct a phone’s orientation by tracking the rotation sensor in a phone.)
2017.06.27 View 7525 -
Face Recognition System 'K-Eye' Presented by KAIST
Artificial intelligence (AI) is one of the key emerging technologies. Global IT companies are competitively launching the newest technologies and competition is heating up more than ever. However, most AI technologies focus on software and their operating speeds are low, making them a poor fit for mobile devices. Therefore, many big companies are investing to develop semiconductor chips for running AI programs with low power requirements but at high speeds.
A research team led by Professor Hoi-Jun Yoo of the Department of Electrical Engineering has developed a semiconductor chip, CNNP (CNN Processor), that runs AI algorithms with ultra-low power, and K-Eye, a face recognition system using CNNP. The system was made in collaboration with a start-up company, UX Factory Co.
The K-Eye series consists of two types: a wearable type and a dongle type. The wearable type device can be used with a smartphone via Bluetooth, and it can operate for more than 24 hours with its internal battery. Users hanging K-Eye around their necks can conveniently check information about people by using their smartphone or smart watch, which connects K-Eye and allows users to access a database via their smart devices. A smartphone with K-EyeQ, the dongle type device, can recognize and share information about users at any time.
When recognizing that an authorized user is looking at its screen, the smartphone automatically turns on without a passcode, fingerprint, or iris authentication. Since it can distinguish whether an input face is coming from a saved photograph versus a real person, the smartphone cannot be tricked by the user’s photograph.
The K-Eye series carries other distinct features. It can detect a face at first and then recognize it, and it is possible to maintain “Always-on” status with low power consumption of less than 1mW. To accomplish this, the research team proposed two key technologies: an image sensor with “Always-on” face detection and the CNNP face recognition chip.
The first key technology, the “Always-on” image sensor, can determine if there is a face in its camera range. Then, it can capture frames and set the device to operate only when a face exists, reducing the standby power significantly. The face detection sensor combines analog and digital processing to reduce power consumption. With this approach, the analog processor, combined with the CMOS Image Sensor array, distinguishes the background area from the area likely to include a face, and the digital processor then detects the face only in the selected area. Hence, it becomes effective in terms of frame capture, face detection processing, and memory usage.
The second key technology, CNNP, achieved incredibly low power consumption by optimizing a convolutional neural network (CNN) in the areas of circuitry, architecture, and algorithms. First, the on-chip memory integrated in CNNP is specially designed to enable data to be read in a vertical direction as well as in a horizontal direction. Second, it has immense computational power with 1024 multipliers and accumulators operating in parallel and is capable of directly transferring the temporal results to each other without accessing to the external memory or on-chip communication network. Third, convolution calculations with a two-dimensional filter in the CNN algorithm are approximated into two sequential calculations of one-dimensional filters to achieve higher speeds and lower power consumption.
With these new technologies, CNNP achieved 97% high accuracy but consumed only 1/5000 power of the GPU. Face recognition can be performed with only 0.62mW of power consumption, and the chip can show higher performance than the GPU by using more power.
These chips were developed by Kyeongryeol Bong, a Ph. D. student under Professor Yoo and presented at the International Solid-State Circuit Conference (ISSCC) held in San Francisco in February. CNNP, which has the lowest reported power consumption in the world, has achieved a great deal of attention and has led to the development of the present K-Eye series for face recognition.
Professor Yoo said “AI - processors will lead the era of the Fourth Industrial Revolution. With the development of this AI chip, we expect Korea to take the lead in global AI technology.”
The research team and UX Factory Co. are preparing to commercialize the K-Eye series by the end of this year. According to a market researcher IDC, the market scale of the AI industry will grow from $127 billion last year to $165 billion in this year.
(Photo caption: Schematic diagram of K-Eye system)
2017.06.14 View 16999 -
Mutations Unveiled that Predispose Lung Cancer Cells to Refractory Histologic Transformation
Cancer pedigree analysis reveals the mutations in RB1 and TP53 genes play a key role in treatment-resistant, cancer cell-type transformation during EGFR inhibitor therapy for lung cancers.
Research led by Korean medical scientists has discovered that a specific type of drug resistance mechanism to EGFR inhibitor therapy in lung cancer is predisposed by mutations in two canonical cancer-related genes: RB1 and TP53. Published in Journal of Clinical Oncology on May 12, the study also found those mutations can be detectable in patients' tumors at the point of clinical diagnosis. Therefore, it can be used as strong markers in clinic for predicting poor outcome for the targeted treatment for lung adenocarcinoma.
Lung adenocarcinoma is the most common type of lung cancer, and about 15% of patients in Western countries and 50% of patients in Asian countries have mutations in the EGFR gene, which is critical for the development of lung cancer. Patients with lung adenocarcinoma harboring the EGFR mutation show favorable responses to EGFR inhibitors such as erlotinib (Tarceva) or gefitinib (Iressa), but ultimately relapse with drug-resistant tumors. Since the initial report in 2006, it has been known that in about 5~15% of patients, the lung adenocarcinoma cells undergo a mysterious transformation into a very different cancer cell type called “small cell lung cancer,” a much more aggressive lung cancer subtype, common in cigarette smokers.
To find out the genetic basis of this process, the researchers compared the genome sequences of multiple cancer tissues acquired during the treatment courses of patients whose tumors underwent small-cell transformation. They reconstructed the cancer cell pedigree by comparing mutations between cancer tissues, and identified that RB1 and TP53 genes are completely inactivated by mutations already in their lung adenocarcinoma tissues.
"We tried to compare the somatic mutational profile of pre-EGFR inhibitor treatment lung adenocarcinomas and post-treatment small cell carcinomas and to reconstruct the pedigrees of the cancer evolution in each patient. Strikingly, both copies of RB1 and TP53 genes were already inactivated at the stage of lung adenocarcinomas in all sequenced cases," said Dr. Jake June-Koo Lee, the first author from KAIST.
They further pursued the clinical implications of RB1 and TP53 inactivation by investigating 75 EGFR-mutated lung adenocarcinoma tissues from patients who received EGFR inhibitor therapy, including patients with small-cell transformation. In this analysis, the lung adenocarcinomas with a complete inactivation of both RB1 and TP53 genes tended to have a 43-times greater risk of transformation into small cell lung cancer during their EGFR inhibitor treatment courses.
Dr. Young Seok Ju, the co-last author from KAIST, explained, "This study shows the power of entire genome analyses to better understand the mechanisms underlying mysterious phenomenon encountered in clinic. Upon accurate bioinformatics, we are finding cancer-specific somatic mutations from the whole-genomes of patients’ cancer cells. These mutations allow us to track the evolution of cancer cells throughout the extraordinary clinical course of a special set of lung cancers."
The complete inactivation of both RB1 and TP53 tumor suppressor genes is found in a minor (<10%) subset of lung adenocarcinoma. This study suggests that the clinical course against targeted therapy is endogenously different for the cancers in the subgroup, and specific drug-resistance mechanisms are predisposed by the two genetic mutations. Indeed, RB1 and TP53 double inactivation is a genetic hallmark of primary small cell lung cancer, observed in nearly all cases.
"We are actively investigating patient tumor tissues to develop optimal surveillance plans and treatment options for patients with lung adenocarcinomas more prone to small-cell transformation," said Dr. Tae Min Kim, the co-last author from Seoul National University Hospital.
The researchers are implementing their findings into lung cancer clinics by screening the RB1 and TP53 mutational status in lung adenocarcinoma patients receiving EGFR inhibitor treatment, and following their treatment courses to develop a treatment strategy for those patients.
This research (doi.org/10.1200/JCO.2016.71.9096) was funded by the National Research Foundation of Korea (NRF-2013H1A2A1032691 to J.-K.L., NRF-2014R1A2A2A05003665 to Y.T.K.); Korea Institute of Science and Technology Information (K-16-L03-C02-S02 to J.L.); and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, which was funded by the Ministry of Health and Welfare (HI14C1234 to T.M.K., HI16C2387 to Y.S.J.)
Figure. Phylogeny analysis of serially-acquired tumors
A. Phylogeny trees of sequenced cases (LC1−LC4) are reconstructed from the WGS data. Conceptual illustrations are depicted with grey color. Circles indicate major clones of the tumors. The length of each branch is proportional to the number of mutations that occurred in the branch. Mutations of cancer-related genes in each branch are indicated with arrows. The time points of relevant treatments are summarized below the trees.
B. Mutations of RB1 and TP53 in two early LADCs (LC1b and LC4a) are visualized using Integrative Genomics Viewer (left panel). Allele-specific copy number analysis shows loss of heterozygosity of chromosomes 13 and 17 in both early LADCs and EGFR TKI-resistant SCLCs (right panel).
C. Clonal evolution of LC1 is described with clinical history and tumor volumes. The horizontal axis represents the time from the diagnosis (0), and the vertical axis indicates the volume of tumors calculated from the computed tomography images.
Abbreviations: LADC, lung adenocarcinoma; SCLC, small cell lung cancer
2017.06.07 View 8939 -
Bio-based p-Xylene Oxidation into Terephthalic Acid by Engineered E.coli
KAIST researchers have established an efficient biocatalytic system to produce terephthalic acid (TPA) from p-xylene (pX). It will allow this industrially important bulk chemical to be made available in a more environmentally-friendly manner.
The research team developed metabolically engineered Escherichia coli (E.coli) to biologically transform pX into TPA, a chemical necessary in the manufacturing of polyethylene terephthalate (PET). This biocatalysis system represents a greener and more efficient alternative to the traditional chemical methods for TPA production. This research, headed by Distinguished Professor Sang Yup Lee, was published in Nature Communications on May 31.
The research team utilized a metabolic engineering and synthetic biology approach to develop a recombinant microorganism that can oxidize pX into TPA using microbial fermentation. TPA is a globally important chemical commodity for manufacturing PET. It can be applied to manufacture plastic bottles, clothing fibers, films, and many other products. Currently, TPA is produced from pX oxidation through an industrially well-known chemical process (with a typical TPA yield of over 95 mol%), which shows, however, such drawbacks as intensive energy requirements at high temperatures and pressure, usage of heavy metal catalysts, and the unavoidable byproduct formation of 4-carboxybenzaldehyde.
The research team designed and constructed a synthetic metabolic pathway by incorporating the upper xylene degradation pathway of Pseudomonas putida F1 and the lower p-toluene sulfonate pathway of Comamonas testosteroni T-2, which successfully produced TPA from pX in small-scale cultures, with the formation of p-toluate (pTA) as the major byproduct. The team further optimized the pathway gene expression levels by using a synthetic biology toolkit, which gave the final engineered E. coli strain showing increased TPA production and the complete elimination of the byproduct.
Using this best-performing strain, the team designed an elegant two-phase (aqueous/organic) fermentation system for TPA production on a larger scale, where pX was supplied in the organic phase. Through a number of optimization steps, the team ultimately achieved production of 13.3 g TPA from 8.8 g pX, which represented an extraordinary yield of 97 mol%.
The team has developed a microbial biotechnology application which is reportedly the first successful example of the bio-based production of TPA from pX by the microbial fermentation of engineered E. coli. This bio-based TPA technology presents several advantages such as ambient reaction temperature and pressure, no use of heavy metals or other toxic chemicals, the removable of byproduct formation, and it is 100% environmentally compatible.
Professor Lee said, “We presented promising biotechnology for producing large amounts of the commodity chemical TPA, which is used for PET manufacturing, through metabolically engineered gut bacterium. Our research is meaningful in that it demonstrates the feasibility of the biotechnological production of bulk chemicals, and if reproducible when up-scaled, it will represent a breakthrough in hydrocarbon bioconversions.”
Ph.D. candidate Zi Wei Luo is the first author of this research (DOI:10.1038/ncomms15689).The research was supported by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) of the Ministry of Science, ICT & Future Planning through the National Research Foundation of Korea.
Figure: Biotransformation of pX into TPA by engineered E. coli.
This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced TPA from pX. The engineered E. coli was developed through reconstituting a synthetic metabolic pathway for pX conversion to TPA and optimized for increased TPA yield and byproduct elimination. Two-phase partitioning fermentation system was developed for demonstrating the feasibility of large-scale production of TPA from pX using the engineered E. coli strains, where pX was supplied in the organic phase and TPA was produced in the aqueous phase.
2017.06.05 View 11894 -
Observation of the Phase Transition of Liquid Crystal Defects
KAIST researchers observed the phase transition of topological defects formed by liquid crystal (LC) materials for the first time.
The phase transition of topological defects, which was also the theme of the Nobel Prize for Physics in 2016, can be difficult to understand for a layperson but it needs to be studied to understand the mysteries of the universe or the underlying physics of skyrmions, which have intrinsic topological defects.
If the galaxy is taken as an example in the universe, it is difficult to observe the topological defects because the system is too large to observe some changes over a limited period of time. In the case of defect structures formed by LC molecules, they are not only a suitable size to observe with an optical microscope, but also the time period in which the phase transition of a defect occurring can be directly observed over a few seconds, which can be extended to a few minutes. The defect structures formed by LC material have radial, circular, or spiral shapes centering on a singularity (defect core), like the singularity that was already introduced in the famous movie "Interstellar,” which is the center point of black hole.
In general, LC materials are mainly used in liquid crystal displays (LCDs) and optical sensors because it is easy to control their specific orientation and they have fast response characteristics and huge anisotropic optical properties. It is advantageous in terms of the performance of LCDs that the defects of the LC materials are minimized. The research team led by Professor Dong Ki Yoon in the Graduate School of Nanoscience and Technology did not simply minimize such defects but actively tried to use the LC defects as building blocks to make micro- and nanostructures for the patterning applications. During these efforts, they found the way to directly study the phase transition of topological defects under in-situ conditions.
Considering the LC material from the viewpoint of a device like a LCD, robustness is important. Therefore, the LC material is injected through the capillary phenomenon between a rigid two-glass plate and the orientation of the LCs can be followed by the surface anchoring condition of the glass substrate. However, in this conventional case, it is difficult to observe the phase transition of the LC defect due to this strong surface anchoring force induced by the solid substrate.
In order to solve this problem, the research team designed a platform, in which the movement of the LC molecules was not restricted, by forming a thin film of LC material on water, which is like oil floating on water. For this, a droplet of LC material was dripped onto water and spread to form a thin film. The topological defects formed under this circumstance could show the thermal phase transition when the temperature was changed. In addition, this approach can trace back the morphology of the original defect structure from the sequential changes during the temperature changes, which can give hints to the study of the formation of topological defects in the cosmos or skyrmions.
Prof. Yoon said, “The study of LC crystal defects itself has been extensively studied by physicists and mathematicians for about 100 years. However, this is the first time that we have observed the phase transition of LC defects directly.” He also added, "Korea is leading in the LCD industry, but our basic research on LCs is not at the world's research level."
The first author of this study is Dr. Min-Jun Gimand supported by a grant from the National Research Foundation (NRF) and funded by the Korean Government (MSIP). The research result was published on May 30, 2017 in Nature Communications.
Figure 1. The phase transition of the LC topological defect on cooling.
Figure 2. Polarizing optical microscopy images of topological defects depending on the strength of the director field. (a,b,e) Convergent director field arrangements of LC molecules and corresponding schematic images; (c,d,f) Divergent director field arrangements of LC molecules and corresponding schematic images.
2017.06.02 View 10102 -
Augmented Reality Application for Smart Tour
‘K-Culture Time Machine,’ an augmented and virtual reality application will create a new way to take a tour. Prof. Woon-taek Woo's research team of Graduate School of Culture Technology of KAIST developed AR/VR application for smart tourism.
The 'K-Culture Time Machine' application (iOS App Store app name: KCTM) was launched on iOS App Store in Korea on May 22 as a pilot service that is targetting the Changdeokgung Palace of Seoul.
The application provides remote experience over time and space for cultural heritage or relics thorough wearable 360-degree video. Users can remotely experience cultural heritage sites with 360-degree video provided by installing a smartphone in a smartphone HMD device, and can search information on historical figures, places, and events related to cultural heritage. Also, 3D reconstruction of lost cultural heritage can be experienced.
Without using wearable HMD devices, mobile-based cultural heritage guides can be provided based on the vision-based recognition on the cultural heritages. Through the embedded camera in smartphone, the application can identify the heritages and provide related information and contents of the hertages. For example, in Changdeokgung Palace, a user can move inside the Changdeokgung Palace from Donhwa-Gate (the main gate of the Changdeokgung Palace), Injeong-Jeon(main hall), Injeong-Moon (Main gate of Injeong-Jeon), and to Huijeongdang (rest place for the king). Through the 360 degree panoramic image or video, the user can experience the virtual scene of heritages.
The virtual 3D reconstruction of the seungjeongwon (Royal Secretariat) which does not exist at present can be shown of the east side of the Injeong-Jeon The functions can be experienced on a smartphone without a wearable device, and it would be a commercial application that can be utilized in the field once the augmented reality function which is under development is completed.
Professor Woo and his research team constructed and applied standardized metadata of cultural heritage database and AR/VR contents. Through this standardized metadata, unlike existing applications which are temporarily consumed after development, reusable and interoperable contents can be made.Professor Woo said, "By enhancing the interoperability and reusability of AR contents, we will be able to preoccupy new markets in the field of smart tourism."
The research was conducted through the joint work with Post Media (CEO Hong Seung-mo) in the CT R&D project of the Ministry of Culture, Sports and Tourism of Korea. The results of the research will be announced through the HCI International 2017 conference in Canada this July.
Figure 1. 360 degree panorama image / video function screen of 'K-Culture Time Machine'. Smartphone HMD allows users to freely experience various cultural sites remotely.
Figure 2. 'K-Culture Time Machine' mobile augmented reality function screen. By analyzing the location of the user and the screen viewed through the camera, information related to the cultural heritage are provided to enhance the user experience.
Figure 3. The concept of 360-degree panoramic video-based VR service of "K-Culture Time Machine", a wearable application supporting smart tour of the historical sites. Through the smartphone HMD, a user can remotely experience cultural heritage sites and 3D reconstruction of cultural heritage that does not currently exist.
2017.05.30 View 11846 -
Extreme Materials for Fusion with Metal Cocktail
The research team under Professor Ryu Ho-jin of the Department of Nuclear and Quantum Engineering has developed a new material for facing fusion plasma environments using metal powder mixing technology. This technology is expected to extend the range of materials that can be designed for use in extreme environments such as in fusion power generators.
The durability of the tokamak vessel, which holds high-temperature plasma, is very important to create fusion power reactors, which are expected to be a future energy source. Currently, high-melting-point metals, such as tungsten, are considered plasma-facing materials to protect the tokamak vessel. However, high-energy thermal shocks, plasma ions, and neutrons are fatal to the plasma-facing material during high temperature fusion plasma operation. Therefore, it is necessary to develop new high-performance materials.
The ITER project, in which seven countries including the United States, the EU, and Korea participate jointly, is constructing a nuclear fusion experimental reactor in France with the goal of achieving the first plasma in 2025 and deuterium-tritium fusion operation in 2035. In Korea, the KSTAR tokamak at the National Fusion Research Institute has succeeded in maintaining high-performance plasma for 70 seconds.
Researchers in Europe, the United States, and China, who are leading the research on fusion plasma-facing materials, are studying the improvement of physical properties by adding a small amount of metal elements to tungsten. However, Professor Ryu’s team reported that by mixing various metals’ powders, including tungsten, they have succeeded in producing a new material that has twice the hardness and strength of tungsten. The difference in the atomic sizes of the well-mixed elements in the alloy is very significant because it makes it difficult to deform the alloy.
The team will continue its research to find alloying compositions that optimize mechanical properties as well as thermal conductivity, plasma interactions, neutron irradiation embrittlement, tritium absorption, and high-temperature oxidation properties.
Professor Ryu said, "Fusion plasma-facing materials are exposed to extreme environments and no metal is capable of withstanding thermal shock, plasma, and neutron damage simultaneously. As a result of this research, attempts to develop complex metallic materials for nuclear fusion and nuclear power are expected to become more active around the world. "
Ph.D. candidate Owais Ahmed Waseem is the first author of this project. The research is supported by the Ministry of Science, ICT and Future Planning, the Korea Research Foundation's Fusion Basic Research project, and the Engineering Research Center. The results were published in 'Scientific Report' on May 16.
Figure 1. Tungsten-based high strengh alloy sample
Figure 2. Fusion plasma facing material development by powder processing of refractory elements
2017.05.26 View 9748