Showing papers by "Korea University published in 2020"

Pan-cancer analysis of whole genomes

Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

Persulfate-Based Advanced Oxidation: Critical Assessment of Opportunities and Roadblocks.

Abstract: Reports that promote persulfate-based advanced oxidation process (AOP) as a viable alternative to hydrogen peroxide-based processes have been rapidly accumulating in recent water treatment literature. Various strategies to activate peroxide bonds in persulfate precursors have been proposed and the capacity to degrade a wide range of organic pollutants has been demonstrated. Compared to traditional AOPs in which hydroxyl radical serves as the main oxidant, persulfate-based AOPs have been claimed to involve different in situ generated oxidants such as sulfate radical and singlet oxygen as well as nonradical oxidation pathways. However, there exist controversial observations and interpretations around some of these claims, challenging robust scientific progress of this technology toward practical use. This Critical Review comparatively examines the activation mechanisms of peroxymonosulfate and peroxydisulfate and the formation pathways of oxidizing species. Properties of the main oxidizing species are scrutinized and the role of singlet oxygen is debated. In addition, the impacts of water parameters and constituents such as pH, background organic matter, halide, phosphate, and carbonate on persulfate-driven chemistry are discussed. The opportunity for niche applications is also presented, emphasizing the need for parallel efforts to remove currently prevalent knowledge roadblocks.

Anomalous absorption of electromagnetic waves by 2D transition metal carbonitride Ti3CNTx (MXene)

Abstract: Lightweight, ultrathin, and flexible electromagnetic interference (EMI) shielding materials are needed to protect electronic circuits and portable telecommunication devices and to eliminate cross-talk between devices and device components. Here, we show that a two-dimensional (2D) transition metal carbonitride, Ti3CNTx MXene, with a moderate electrical conductivity, provides a higher shielding effectiveness compared with more conductive Ti3C2Tx or metal foils of the same thickness. This exceptional shielding performance of Ti3CNTx was achieved by thermal annealing and is attributed to an anomalously high absorption of electromagnetic waves in its layered, metamaterial-like structure. These results provide guidance for designing advanced EMI shielding materials but also highlight the need for exploring fundamental mechanisms behind interaction of electromagnetic waves with 2D materials.

Subwavelength dielectric resonators for nonlinear nanophotonics

Abstract: Subwavelength optical resonators made of high-index dielectric materials provide efficient ways to manipulate light at the nanoscale through mode interferences and enhancement of both electric and magnetic fields. Such Mie-resonant dielectric structures have low absorption, and their functionalities are limited predominantly by radiative losses. We implement a new physical mechanism for suppressing radiative losses of individual nanoscale resonators to engineer special modes with high quality factors: optical bound states in the continuum (BICs). We demonstrate that an individual subwavelength dielectric resonator hosting a BIC mode can boost nonlinear effects increasing second-harmonic generation efficiency. Our work suggests a route to use subwavelength high-index dielectric resonators for a strong enhancement of light-matter interactions with applications to nonlinear optics, nanoscale lasers, quantum photonics, and sensors.

Bipolar-shell resurfacing for blue LEDs based on strongly confined perovskite quantum dots

Abstract: Colloidal quantum dot (QD) solids are emerging semiconductors that have been actively explored in fundamental studies of charge transport1 and for applications in optoelectronics2. Forming high-quality QD solids—necessary for device fabrication—requires substitution of the long organic ligands used for synthesis with short ligands that provide increased QD coupling and improved charge transport3. However, in perovskite QDs, the polar solvents used to carry out the ligand exchange decompose the highly ionic perovskites4. Here we report perovskite QD resurfacing to achieve a bipolar shell consisting of an inner anion shell, and an outer shell comprised of cations and polar solvent molecules. The outer shell is electrostatically adsorbed to the negatively charged inner shell. This approach produces strongly confined perovskite QD solids that feature improved carrier mobility (≥0.01 cm2 V−1 s−1) and reduced trap density relative to previously reported low-dimensional perovskites. Blue-emitting QD films exhibit photoluminescence quantum yields exceeding 90%. By exploiting the improved mobility, we have been able to fabricate CsPbBr3 QD-based efficient blue and green light-emitting diodes. Blue devices with reduced trap density have an external quantum efficiency of 12.3%; the green devices achieve an external quantum efficiency of 22%. A solution-based ligand-exchange strategy enables the realization of close-packed quantum dot solid films with near-unity photoluminescence quantum yield and high charge carrier mobility.

Multifunctional sonosensitizers in sonodynamic cancer therapy

Abstract: Phototherapy, including photodynamic therapy and photothermal therapy, has the potential to treat several types of cancer. However, to be an effective anticancer treatment, it has to overcome limitations, such as low penetration depth, low target specificity, and resistance conferred by the local tumor microenvironment. As a non-invasive technique, low-intensity ultrasound has been widely used in clinical diagnosis as it exhibits deeper penetration into the body compared to light. Recently, sonodynamic therapy (SDT), a combination of low-intensity ultrasound with a chemotherapeutic agent (sonosensitizer), has been explored as a promising alternative for cancer therapy. As all known cancer treatments such as chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, and drug delivery have been advanced independently enough to complement others substantially, the combination of these therapeutic modalities with SDT is opportune. This review article highlights the recent advances in SDT in terms of sonosensitizers and their formulations and anticancer therapeutic efficacy. Also discussed is the potential of SDT in combination with other modalities to address unmet needs in precision medicine.

Electromagnetic Shielding of Monolayer MXene Assemblies.

Abstract: Miniaturization of electronics demands electromagnetic interference (EMI) shielding of nanoscale dimension. The authors report a systematic exploration of EMI shielding behavior of 2D Ti3 C2 Tx MXene assembled films over a broad range of film thicknesses, monolayer by monolayer. Theoretical models are used to explain the shielding mechanism below skin depth, where multiple reflection becomes significant, along with the surface reflection and bulk absorption of electromagnetic radiation. While a monolayer assembled film offers ≈20% shielding of electromagnetic waves, a 24-layer film of ≈55 nm thickness demonstrates 99% shielding (20 dB), revealing an extraordinarily large absolute shielding effectiveness (3.89 × 106 dB cm2 g-1 ). This remarkable performance of nanometer-thin solution processable MXene proposes a paradigm shift in shielding of lightweight, portable, and compact next-generation electronic devices.

Machine Learning for Molecular Simulation.

Abstract: Machine learning (ML) is transforming all areas of science. The complex and time-consuming calculations in molecular simulations are particularly suitable for an ML revolution and have already been profoundly affected by the application of existing ML methods. Here we review recent ML methods for molecular simulation, with particular focus on (deep) neural networks for the prediction of quantum-mechanical energies and forces, on coarse-grained molecular dynamics, on the extraction of free energy surfaces and kinetics, and on generative network approaches to sample molecular equilibrium structures and compute thermodynamics. To explain these methods and illustrate open methodological problems, we review some important principles of molecular physics and describe how they can be incorporated into ML structures. Finally, we identify and describe a list of open challenges for the interface between ML and molecular simulation.

Metal contamination and bioremediation of agricultural soils for food safety and sustainability

Abstract: Agricultural soil is a non-renewable natural resource that requires careful stewardship in order to achieve the United Nations’ Sustainable Development Goals However, industrial and agricultural activity is often detrimental to soil health and can distribute heavy metal(loid)s into the soil environment, with harmful effects on human and ecosystem health In this Review, we examine processes that can lead to the contamination of agricultural land with heavy metal(loid)s, which range from mine tailings runoff entering local irrigation channels to the atmospheric deposition of incinerator and coal-fired power-plant emissions We discuss the relationship between heavy metal(loid) biogeochemical transformations in the soil and their bioavailability We then review two biological solutions for remediation of contaminated agricultural land, plant-based remediation and microbial bioremediation, which offer cost-effective and sustainable alternatives to traditional physical or chemical remediation technologies Finally, we discuss how integrating these innovative technologies with profitable and sustainable land use could lead to green and sustainable remediation strategies, and conclude by identifying research challenges and future directions for the biological remediation of agricultural soils Contamination of agricultural soils by heavy metals and metalloids has severe consequences on human and ecosystem health This Review discusses the sources of heavy metal(loid) contamination, the mechanisms by which these contaminants interact with biological and geochemical soil elements, and plant-based and microorganism-based remediation strategies

Emerging combination strategies with phototherapy in cancer nanomedicine

Abstract: Optical techniques using developed laser and optical devices have made a profound impact on modern medicine, with "biomedical optics" becoming an emerging field. Sophisticated technologies have been developed in cancer nanomedicine, such as photothermal therapy and photodynamic therapy, among others. However, single-mode phototherapy cannot completely treat persistent tumors, with the challenges of relapse or metastasis remaining; therefore, combinatorial strategies are being developed. In this review, the role of light in cancer therapy and the challenges of phototherapy are discussed. The development of combinatorial strategies with other therapeutic methods, including chemotherapy, immunotherapy, gene therapy, and radiotherapy, is presented and future directions are further discussed. This review aims to highlight the significance of light in cancer therapy and discuss the combinatorial strategies that show promise in addressing the challenges of phototherapy.

Advances in the Cathode Materials for Lithium Rechargeable Batteries.

Abstract: The accelerating development of technologies requires a significant energy consumption, and consequently the demand for advanced energy storage devices is increasing at a high rate. In the last two decades, lithium-ion batteries have been the most robust technology, supplying high energy and power density. Improving cathode materials is one of the ways to satisfy the need for even better batteries. Therefore developing new types of positive electrode materials by increasing cell voltage and capacity with stability is the best way towards the next-generation Li rechargeable batteries. To achieve this goal, understanding the principles of the materials and recognizing the problems confronting the state-of-the-art cathode materials are essential prerequisites. This Review presents various high-energy cathode materials which can be used to build next-generation lithium-ion batteries. It includes nickel and lithium-rich layered oxide materials, high voltage spinel oxides, polyanion, cation disordered rock-salt oxides and conversion materials. Particular emphasis is given to the general reaction and degradation mechanisms during the operation as well as the main challenges and strategies to overcome the drawbacks of these materials.

Nanoarchitectured Structure and Surface Biofunctionality of Mesoporous Silica Nanoparticles

Abstract: Mesoporous silica nanoparticles (MSNs), one of the important porous materials, have garnered interest owing to their highly attractive physicochemical features and advantageous morphological attributes. They are of particular importance for use in diverse fields including, but not limited to, adsorption, catalysis, and medicine. Despite their intrinsic stable siliceous frameworks, excellent mechanical strength, and optimal morphological attributes, pristine MSNs suffer from poor drug loading efficiency, as well as compatibility and degradability issues for therapeutic, diagnostic, and tissue engineering purposes. Collectively, the desirable and beneficial properties of MSNs have been harnessed by modifying the surface of the siliceous frameworks through incorporating supramolecular assemblies and various metal species, and through incorporating supramolecular assemblies and various metal species and their conjugates. Substantial advancements of these innovative colloidal inorganic nanocontainers drive researchers in promoting them toward innovative applications like stimuli (light/ultrasound/magnetic)-responsive delivery-associated therapies with exceptional performance in vivo. Here, a brief overview of the fabrication of siliceous frameworks, along with discussions on the significant advances in engineering of MSNs, is provided. The scope of the advancement in terms of structural and physicochemical attributes and their effects on biomedical applications with a particular focus on recent studies is emphasized. Finally, interesting perspectives are recapitulated, along with the scope toward clinical translation.

Virtual Reality Sickness: A Review of Causes and Measurements

Abstract: In virtual reality (VR), users can experience symptoms of motion sickness, which is referred to as VR sickness or cybersickness. The symptoms include but are not limited to eye fatigue, disorientat...

Extraction and validation of a new set of CMS pythia8 tunes from underlying-event measurements

Abstract: New sets of CMS underlying-event parameters (“tunes”) are presented for the pythia8 event generator. These tunes use the NNPDF3.1 parton distribution functions (PDFs) at leading (LO), next-to-leading (NLO), or next-to-next-to-leading (NNLO) orders in perturbative quantum chromodynamics, and the strong coupling evolution at LO or NLO. Measurements of charged-particle multiplicity and transverse momentum densities at various hadron collision energies are fit simultaneously to determine the parameters of the tunes. Comparisons of the predictions of the new tunes are provided for observables sensitive to the event shapes at LEP, global underlying event, soft multiparton interactions, and double-parton scattering contributions. In addition, comparisons are made for observables measured in various specific processes, such as multijet, Drell–Yan, and top quark-antiquark pair production including jet substructure observables. The simulation of the underlying event provided by the new tunes is interfaced to a higher-order matrix-element calculation. For the first time, predictions from pythia8 obtained with tunes based on NLO or NNLO PDFs are shown to reliably describe minimum-bias and underlying-event data with a similar level of agreement to predictions from tunes using LO PDF sets.

A Phase 2 Multi-institutional Study of Nivolumab for Patients with Advanced Refractory Biliary Tract Cancer

Abstract: Importance Currently, there is no established second-line systemic treatment for biliary tract cancer (BTC). Preclinical data have demonstrated that the presence of tumor-infiltrating CD8 T cells and programmed cell death 1 ligand 1–expressing tumor cells in the tumor microenvironment of BTC supports the rationale of using programmed cell death 1 protein blockade immunotherapy in BTC. Objective To evaluate anticancer activity of nivolumab in patients with advanced refractory BTC. Design, Setting, and Participants In this single-group, multicenter phase 2 study of nivolumab, 54 patients with histologically confirmed BTC whose disease progressed while undergoing treatment with at least 1 line but no more than 3 lines of systemic therapy were enrolled between October 5, 2016, and December 26, 2018. Analysis was performed on an intention-to-treat basis. Interventions Nivolumab, 240 mg, was delivered intravenously every 2 weeks for 16 weeks, and then 480 mg was delivered intravenously every 4 weeks until disease progression or unacceptable toxic effects occurred. Main Outcomes and Measures The primary end point was investigator-assessed objective response rate, and the secondary end points were progression-free survival, overall survival, and incidence of adverse events. Results A total of 54 patients (27 men and 27 women; median age, 65 years [range, 28-86 years]) enrolled, and 46 (22 men and 24 women; median age, 65 years [range, 28-86 years]) were examined for objective response with radiologic imaging. The investigator-assessed objective response rate was 22% (10 of 46), including 1 unconfirmed partial response, with a disease control rate of 59% (27 of 46). Central independent review found an objective response rate of 11% (5 of 46), including 1 unconfirmed partial response, with a disease control rate of 50% (23 of 46). All patients who responded to treated (hereafter referred to as responders) had mismatch repair protein–proficient tumors. The median duration of investigator-assessed response was not reached, with a median follow-up of 12.4 months. Among the intention-to-treat population, median progression-free survival was 3.68 months (95% CI, 2.30-5.69 months) and median overall survival was 14.24 months (95% CI, 5.98 months to not reached). Programmed cell death 1 ligand 1 expression in tumors was associated with prolonged progression-free survival (hazard ratio, 0.23; 95% CI, 0.10-0.51;P Conclusions and Relevance This study found that nivolumab was well tolerated and showed modest efficacy with durable response in patients with refractory BTC. Further studies are warranted to verify the findings and evaluate biomarkers for improved treatment selection for patients. Trial Registration ClinicalTrials.gov Identifier:NCT02829918

A Critical Review on Thin-Film Nanocomposite Membranes with Interlayered Structure: Mechanisms, Recent Developments, and Environmental Applications

Abstract: The separation properties of polyamide reverse osmosis and nanofiltration membranes, widely applied for desalination and water reuse, are constrained by the permeability-selectivity upper bound. Although thin-film nanocomposite (TFN) membranes incorporating nanomaterials exhibit enhanced water permeance, their rejection is only moderately improved or even impaired due to agglomeration of nanomaterials and formation of defects. A novel type of TFN membranes featuring an interlayer of nanomaterials (TFNi) has emerged in recent years. These novel TFNi membranes show extraordinary improvement in water flux (e.g., up to an order of magnitude enhancement) along with better selectivity. Such enhancements can be achieved by a wide selection of nanomaterials, ranging from nanoparticles, one-/two-dimensional materials, to interfacial coatings. The use of nanostructured interlayers not only improves the formation of polyamide rejection layers but also provides an optimized water transport path, which enables TFNi membranes to potentially overcome the longstanding trade-off between membrane permeability and selectivity. Furthermore, TFNi membranes can potentially enhance the removal of heavy metals and micropollutants, which is critical for many environmental applications. This review critically examines the recent developments of TFNi membranes and discusses the underlying mechanisms and design criteria. Their potential environmental applications are also highlighted.

A Multi-Organ Nucleus Segmentation Challenge

Abstract: Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated. Contestants were given a training set with 30 images from seven organs with annotations of 21,623 individual nuclei. A test dataset with 14 images taken from seven organs, including two organs that did not appear in the training set was released without annotations. Entries were evaluated based on average aggregated Jaccard index (AJI) on the test set to prioritize accurate instance segmentation as opposed to mere semantic segmentation. More than half the teams that completed the challenge outperformed a previous baseline. Among the trends observed that contributed to increased accuracy were the use of color normalization as well as heavy data augmentation. Additionally, fully convolutional networks inspired by variants of U-Net, FCN, and Mask-RCNN were popularly used, typically based on ResNet or VGG base architectures. Watershed segmentation on predicted semantic segmentation maps was a popular post-processing strategy. Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics.

Clinical Significance of a High SARS-CoV-2 Viral Load in the Saliva.

Abstract: Background Patients with coronavirus disease 2019 (COVID-19) can unknowingly spread the virus to several people during the early subclinical period. Methods We evaluated the viral dynamics in various body fluid specimens, such as nasopharyngeal swab, oropharyngeal swab, saliva, sputum, and urine specimens, of two patients with COVID-19 from hospital day 1 to 9. Additional samples of the saliva were taken at 1 hour, 2 hours, and 4 hours after using a chlorhexidine mouthwash. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was determined by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Results SARS-CoV-2 was detected from all the five specimens of both patients by rRT-PCR. The viral load was the highest in the nasopharynx (patient 1 = 8.41 log10 copies/mL; patient 2 = 7.49 log10 copies/mL), but it was also remarkably high in the saliva (patient 1 = 6.63 log10 copies/mL; patient 2 = 7.10 log10 copies/mL). SARS-CoV-2 was detected up to hospital day 6 (illness day 9 for patient 2) from the saliva of both patients. The viral load in the saliva decreased transiently for 2 hours after using the chlorhexidine mouthwash. Conclusion SARS-CoV-2 viral load was consistently high in the saliva; it was relatively higher than that in the oropharynx during the early stage of COVID-19. Chlorhexidine mouthwash was effective in reducing the SARS-CoV-2 viral load in the saliva for a short-term period.